-K. P. Muzumdar.
A pharmacy is both a professional and a commercial institution; hence the pharmacist must be familiar with the laws governing his activities as a professional practitioner as well as a business man. He should have working knowledge of the State and Central Government laws a well as local regulations. He must also be aware of the laws of negligence, as set forth in common law or by Statute. A druggist is responsible if anyone is injured by the negligent act of himself or his agent, provided such act is done within the scope of the agent’s real or apparent authority. Negligence is absence of proper care. What is proper care is a question that depends on the facts in each case.
The manufacture, sale and distribution of homoeopathic medicines are governed mainly by the Drug and Cosmetics Act and the Rules thereunder’ the Drugs & Magic Remedies (objectionable Advertisements) Act; the Medicinal and Toilet preparations (Excise Duties) Act and Dangerous Drugs Rules, as amended from time to time.
Drugs & Cosmetics Act 1940 (XXIII of 1940) & Drugs and Cosmetics Rules 1945: (amended) 1969 Effection 6-12-69.
This legislation regulates the import, the manufacture, and the sale of drugs (including homoeopathic medicines).
Rule 2 (dd) defines “Homoeopathic medicines” as follows: “(dd) Homoeopathic medicines include any drug which is recorded in Homoeopathic provings or therapeutic efficacy of which has been established through long clinical experiences as recorded in authoritative Homoeopathic literature of India and abroad and which is prepared according to the techniques of Homoeopathic pharmacy and covers combination of ingredients of such Homoeopathic medicines but does not include a medicine which is administered by parenteral route.”
Provisions relating to sale of Homoeopathic Medicines are included in part VI-A, those relating to manufacture for sale are included under part VII-A, and those relating to labelling and packing under part IX-A. Relevant rules are reproduced below for ready reference.
Part VI-A- Sale of Homoeopathic Medicines
67-A. (1) The State Government shall appoint Licensing Authorities for the purpose of this part for such areas as may be specified.
(2) An application for the grant or renewal of a licence to sell, stock or distribute Homoeopathic Medicines shall be made in From 19-B to the Licensing Authority and shall be accompanied by a fee of rupees five.
Provided that if the applicant applies for renewal of licence after its expiry but within one month of such expiry the fee payable for renewal of such licence shall be rupees five, plus an additional fee of rupees five.
67-B. A Licensing Authority may, with the approval of the State Government by an order in writing, delegate the power to sign licences and such other powers as may be specified, to any other persons under his control.
67-C. Forms of licence to sell drugs – (1) A licence to sell, stock or exhibit for sale, or distribute Homoeopathic Medicines by retail or by wholesale shall be issued in form 20-C or 20-D as the case may be.
67-D. Sale at more than one place-If drugs are sold or stocked for sale at more than one place, a separate application shall be made and a separate licence shall be obtained in respect of each place.
67-E. Duration of licence-An original licence or a renewed licence, unless it is sooner suspended or cancelled shall be valid up to 31st December of the year following the year in which it is granted or renewed.
Provided that if the application for renewal of the licence in force is made before its expiry, or if the application is made and the additional fee paid within one month of its expiry, the licence shall continue to be in force until orders are passed on the application. The licence shall be deemed to have expired, if application for renewal is not made within one month after its expiry.
67-F. Conditions to be satisfied before a licence in Form 20-c or Form 20-D is granted:
(1) A licence in form 20-C or form 20-D to sell, stock or exhibit for sale or distribute Homoeopathic Medicines and who is in the opinion of the Licensing Authority competent to deal in Homoeopathic Medicines.
(2) Any person who is aggrieved by the order passed by the Licensing Authority under sub-rule (1), may within 30 days from the date of the receipt of such order appeal to the State Government and the State Government may, after such enquiry into the matter as it considers necessary and after giving the appellant an opportunity for representing his case, make such order in relation thereto as it thinks fit.
67-G. Conditions of licence-Licence in form 20-c or 20-D shall be subjected to the conditions stated therein and to the following further conditions, namely-
(1) The premises where the Homoeopathic Medicines are stocked for sale or sold, are maintained in clean condition.
(2) The sale of Homoeopathic Medicines shall be conducted under the supervision of a person, competent to deal in Homoeopathic Medicines.
(3) The licensee shall permit an Inspector to inspect the premises and furnish such information as he may require for ascertaining whether the provisions of the Act and the Rules made thereunder have been observed.
(4) The licensees in form 20-D shall maintain records of purchase and sale of Homoeopathic Medicines containing alcohol, together with the names and addresses of parties to whom they are sold.
(5) “The licensee in Form 20-C shall maintain records of purchase and sale of Homoeopathic Medicines containing alcohol. No records of sale in respect of Homoeopathic potentised preparations in containers of 30 ml. or lower capacity and in respect of mother tincture made up in quantities up to 60 ml. need be maintained.”
67-H. Cancellation and suspension of licences-
(1) The Licensing Authority may, after giving the licensee an opportunity to show cause why such an order should not be passed by an order in writing, stating the reasons therefore cancel a licence issued under this Part or suspend for such period as he thinks fit, if in his opinion the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act or the Rules made thereunder.
Provided that if such failure or contravention is the consequence of an act or omission on the part of an agent or employee, the licence shall not be cancelled or suspended unless the Licensing Authority is satisfied-
(a) That the act or omission was instigated or connived at by the owner of the business, or, if the owner is a firm or company, by a partner of the firm or a director of the company, or
(b) That the owner of the business or an agent or employee of the owner had been guilty of a similar act or omission within twelve months before the date on which the act or omission in question took place and that the owner had, or reasonably ought to have had knowledge of that previous act or omission, or
(d) That the owner of the business had not used due vigilance to ensure that the conditions of the licence or provisions of the Act or the Rules made thereunder were observed.
(2) A licensee whose licence has been suspended or cancelled may appeal to the State Government, whose decision shall be final.
Part VII A- Manufacture for Sale of Homoeopathic Medicines:
85 A. Manufacture on more than one set of premises If Homoeopathic Medicines are manufactured in more than one set of premises, a separate application shall be made and a separate licence shall be obtained in respect of each such set of premises.
85 B. Application for licence to manufacture Homoeopathic Medicines.
(1) Application for grant or renewal of licences to manufacture for sale of Homoeopathic Medicines shall be made to the Licensing Authority appointed by the State Government for the purpose of this Part, hereinafter in this Part referred to as the Licensing Authority and shall be made in Form 24-C.
“Applications for licence to manufacture potentised preparations from back potencies by Pharmacies which are already licensed to sell Homoeopathic Medicines by retail shall also be made in Form 24-C and such application shall be accompanied by a fee of rupees twenty.”
(2) The application in Form 24-C shall be accompanied by a fee of rupees forty for manufacture of Homoeopathic mother tincture and potentised preparations, and by a fee of rupees twenty for manufacture of Homoeopathic potentised preparations only.
(3) If a person applies for renewal of a licence after its expiry but within one month of such expiry, the fee payable for the renewal of such a licence shall be (i) rupees forty plus an additional fee of rupees twenty for the manufacture of Homoeopathic mother tinctures and potentised preparations, and (ii) rupees twenty plus an additional fee of rupees ten for the manufacture of Homoeopathic potentised only.
(4) A fee of rupees ten shall be paid for a duplicate copy of the licence for the manufacture of Homoeopathic mother tinctures and potentised preparations issued under sub-rule (1) if the original is defaced, damaged or lost, while the fee to be paid for such a duplicate copy of the licence for the manufacture of Homoeopathic potentised preparations only shall be rupees five.
85-C. Application to manufacture `New Homoeopathic Medicines’- Subject to the other provisions of these Rules-
(1) No `New Homoeopathic Medicine’ shall be manufactured unless it is previously approved by the licensing Authority mentioned in Rule 21.
(2) The manufacturer of `New Homoeopathic Medicines’, when applying to the Licensing Authority mentioned in sub-rule (1) shall produce such documentary and other evidence as may be required by the Licensing Authority for assessing the therapeutic efficacy of the medicine including the minimum provings carried out with it.
(3) While applying for a licence to manufacture `New Homoeopathic Medicine’, an applicant shall produce along with his application evidence that the `New Homoeopathic Medicine’ for the manufacture of which application is made has already been approved.
Explanation-The term `New Homoeopathic Medicine’ in this rule shall have the same meaning as in rule 30-AA.
“85-D. From of Licence to Manufacture Homoeopathic medicines- Licence for manufacture of Homoeopathic medicines as a licence to manufacture potentised preparations from back potencies by Pharmacies which are already licensed to sell Homoeopathic medicines by retail, shall be granted in Form 25-C.”
85-E. Conditions for the grant or renewal of a licence in Form 25-C. Before a licence in Form 25-C is granted or renewed, the following conditions shall be complied with by the applicant:-
(1) The manufacture of Homoeopathic medicines shall be conducted under the directions and supervision of competent technical staff consisting at least of one person who is a whole-time employee and who has at least five years’ experience in the manufacture of Homoeopathic medicines.
(2) “The factory premises shall be clean and the manufacture shall be carried out under hygienic conditions.”
(3) The applicant for manufacture of Homoeopathic mother tinctures shall either (i) provide and maintain adequate staff, premises and laboratory equipment for identifying the raw materials and for testing the mother tinctures wherever possible, or (ii) make arrangements with some institution approved by the Licensing Authority for such tests, wherever possible, to be regularly carried out on his behalf by that institution.
(4) The premises where Homoeopathic medicines are manufactured shall be distinct and separate from the premises used for residential purposes.
(5) Homoeopathic medicines shall not be manufactured simultaneously with drugs pertaining to other systems of medicine.
(6) The applicant shall make arrangements for proper storage of Homoeopathic medicines manufactured by him, provided that in case potentised preparations are made in a Pharmacy holding licence in Form 20-C, the conditions (2) and (3) shall not apply. The licensee shall ensure to the satisfaction of the Licensing Authority that the products manufactured by him, conform to the claims made on the label.
85-F. Duration of Licence-
An original licence or a renewed licence, unless it is sooner suspended or cancelled, shall be valid up to the 31st December of the year following the year in which it is granted or renewed.
Provided that if the application for renewal of licence in force is made before its expiry, or if the application is made and the additional fee paid within one month of its expiry, the licence shall continue to be in force until orders are passed on the application. The licence shall be deemed to have expired if the application for its renewal is not made within one month after its expiry.
85-G. Certificate of Renewal.
The certificate of renewal of a licence in Form 25-C shall be issued in form 26-C.
85-H. Conditions of Licence-
A licence in Form 25-C, shall be subject to the conditions stated therein and to the following further conditions, namely:
(a) the licensee shall provide and maintain staff and premises as specified in rule 85-E.
(b) The Licensing Authority allows that the Inspector is authorized by the Licensing Authority in that behalf to enter with or without prior notice, any premises where the manufacture of a Homoeopathic medicine in respect of which the licence is issued is carried on, to inspect the premises and to take samples of the manufactured Homoeopathic medicines;
(c) the licensee shall allow an Inspector to inspect all registers and records maintained under these rules and shall supply to the Inspector such information as he may require for the purpose of ascertaining whether the provisions of the Act and the rules made thereunder have been observed;
(d) the licensee shall maintain an Inspection Book to enable an Inspector to record his impressions and defects noticed;
(e) the licensee shall comply with the following conditions in respect of mother tinctures manufactured by him.
i) the crude drug used in the manufacture of the mother tincture shall be identified and records of such identification shall be kept;
ii) the total solids in the mother tincture shall be determined and records of the same shall be maintained.
iii) the alcohol content in the mother tincture shall be determined and records of the same shall be maintained.
iv) the containers of the mother tinctures shall preferably be of glass and shall be clean and free from any sort of impurities or adhering matter. The glass shall be neutral as far as possible.
v) in the process of manufacture of mother tincture hygienic conditions shall be scrupulously observed by the licensee. Storage and handing conditions shall also be properly observed by the licensee according to Homoeopathic principles;
(f) records shall be maintained of Homoeopathic medicines containing alcohol and the quantities sold together with the names and addresses of the parties to whom they are sold.
85-I. Cancellation and Suspension of Licence-
(1) The Licensing Authority may, after giving the licensee an opportunity to show cause why such an order should not be passed, by an order in writing, stating the reasons therefore, cancel a licence issued under this part for such period as he thinks fit, either wholly or in respect of some of the substances to which it relates if, in his opinion, the licensee has failed to comply with any of the conditions of the licence or with any provisions of the Act or rules made thereunder.
(2) A licensee whose license has been suspended or cancelled may appeal to the State Government, whose decision shall be final.
Part IX-A – Labelling and Packing of Homoeopathic Medicines:
106-A. Manner of labelling of Homoeopathic medicines
(A) the following particulars shall be either printed or written in indelible ink and shall appear in a conspicuous manner on the label of the innermost container of any Homoeopathic medicine and on every other covering in which the container is packed:
(1) The words `Homoeopathic Medicine’.
(2) The name of the medicine:
(a) For drugs included in the Homoeopathic Pharmacopoeia of the United States or the United Kingdom, the name specified in that Pharmacopoeia.
(b)For other drugs, the name descriptive of the true nature of the drug.
(3) The potency of the Homoeopathic medicine- For this purpose the potency shall be expressed either in decimal, centesimal or millesimal systems.
(4) `Name and address of the manufacturer when sold in original containers of the manufacturer. In case the Homoeopathic medicine is sold in a container other than that of the manufacturer, the name and address of the seller.’
(5) In case the Homoeopathic medicine contains alcohol, the alcohol content in percentage by volume in terms of ethyl alcohol shall be stated on the label:
Provided that in case the total quantity of the Homoeopathic Medicine in the container is 30 millilitre or less, it will not be necessary to state the content of alcohol on the label.
(B) In addition to the above particulars the label of a Homoeopathic mother tincture shall display the following particulars:
(1) A distinctive batch number, that is to say, the number by reference to which details of manufacture of the particular batch from which the substance in the container is taken are recorded and are available for inspection, the figures representing the batch number being preceded by the words `Batch No.’ or `Batch’ or `Lot Number’ or `Lot No.’ or `Lot’ or any.
(2) Manufacturing licence number, the number being preceded by the words `manufacturing Licence Number’ or `Mfg. Lic. No.’ or `M.L.’
(C) No Homoeopathic medicine containing a single ingredient shall bear a proprietary name on its label.
The Drugs and Magic Remedies (Objectionable Advertisements) Act (21 of 1954) and the Rules (1955) thereunder are intended to protect the consumer and prevent the practice of misleading and extravagant claims made in respect of many medicines and especially those claiming as remedies for many diseases considered at present as incurable.
The Medicinal and Toilet Preparations (Excise Duties) Act, 1955, No. 16 of 1955 provides for the levy and collection of duty of excise on medicinal and toilet preparations containing alcohol, opium, Indian hemp or other narcotic drugs or narcotics.
As the homoeopathic medicines comprise mainly of alcohol, a pharmacist must be conversant with the above legislations.
Dangerous Drugs Act:
This legislation relates to medicines containing opium, morphine, pethidine, etc., which are considered addiction forming, dependence producing drugs, and regulates their, manufacture, sale possession, etc.
Drug Prices (Display and Control) Order, 1966:
This order has been made in order to, make drugs available to the general public at fair prices. Any change in the wholesale and retail price of a drug can be effected only with the prior approval of the Central Government. Under a recent amendment to this Order no such prior approval for a change in price is necessary in respect of a drug covered by the latest edition of the Homoeopathic Pharmacopoeias of U.K., U.S.A. and Germany and is without a specific brand name.
Notification: New Delhi, 12th June, 1987.
G. S. R. 570 (E)-Whereas certain draft rules further to amend the Drugs and Cosmetics Rules, 1915, were published, as required by sections 12 and 33 of the Drugs and Cosmetics Act, 1940, under the notification of the Government of India in the Ministry of Health and Family Welfare No. G. S. R. 1050 (E), dated the 29th August, 1986, in the Gazette of India, Extraordinary, Part II Section 3, Sub-Section (i) dated the 29th August, 1986 at the Pages 4 to 7 inviting objections and suggestions from all persons likely to be affected thereby before the expiry of a period of sixty days from the date on which the copies of the Official Gazette containing the said notification were made available to the public;
And whereas copies of the said Gazette were made available to the public on the 29th August 1986.
And whereas the objections and suggestions received from the Public on the said draft have been considered by the Central Government; Now therefore, in exercise of the powers conferred by sections 12 and 33 of the said Act, the Central Government, after consultation with the Drugs Technical Advisory Board, hereby makes the following rules further t amend the Drugs and Cosmetics Rules, 1945, namely:-
1. (1) These rules may be called the Drugs and Cosmetics (SECOND Amendment) Rules, 1987.
(2) They shall come into force on the date of their publication in the Official Gazette.
2. In the drugs and Cosmetics Rules, 1945- (a) In rule 85-E for clause (2) the following clause shall be substituted, namely:- “(2) The factory premises shall comply with the requirements and conditions specified in Schedule M-1: Provided that where the licensing authority considers it necessary or expedient so to do, it may having regard to the nature and extent of manufacturing operations, relax or suitably alter the said requirements or conditions in any particular case for reasons to be recorded in writing;”
(b) After Schedule M the following Schedule shall be inserted, namely:- “SCHEDULE M-1 (See rule 85-E(2)
1. Requirements for factory premises for manufacture of Homoeopathic preparations:
(a) Location and surrounding – The factory shall be situated in a place which shall not be adjacent to an open sewage drain public lavatory or any factory which produces a disagreeable or obnoxious odour or fumes or large quantities of soot, dust or smoke. The factory shall be located in a sanitary place remote from filthy surroundings.
(b) Buildings-The part of the building used for manufacturing shall not be used as a sleeping place and no sleeping place adjoining to it shall communicate therewith except through open air or through an intervening open space. The walls of the room in which manufacturing operations are carried out shall, upto a height of six feet from the floor, be smooth water-proof and shall be capable of being kept clean. The Flooring shall be smooth, even and washable and shall be such as not to permit of retention or accumulation of dust. There shall be no chinks or crevices in the walls of floor.
(c) The building used for the factory shall be constructed so as to permit production under hygienic conditions laid down in the Factories Act, 1948 (63 of 1948).
(d) Water-Supply- The water used in manufacture shall be pure and of drinkable quality free from pathogenic micro-organisms.
(e) Disposal of waste-There should be adequate arrangement for disposal of waste water and other residues from the laboratory.
(f) The rooms should be airy and clean and the temperature of the room should be moderately comfortable.
(g) Health, clothing and Sanitary requirement of the Staff- All workers shall be free from contagious or obnoxious disease. Their clothing shall consist of a white or coloured uniform suitable to the nature of work and the climate, and shall be clean. Adequate facilities for personal cleanliness, such as clean towels, soap and hand scrubbing brushes, shall be provided separately for each sex. The workers shall be required to wash and change into clean footwear before entering the rooms where the manufacturing operations are carried on. Workers shall be required to wear either a clean cap or a suitable headgear so as to avoid any possibility of contamination by hair or perspiration.
(h) Medical services-The manufacturer shall provide adequate facilities for First Aid Medical inspection of workers at the time of employment and periodically check up thereafter at least once a year.
(i) Working benches-Working benches shall be provided for carrying out operations such as fulling,labelling, packing etc. Such benches shall be fitted with smooth, impervious tops capable of being washed.
(j) Container management-Where operations involving use of containers such as bottles, phials and jars are conducted, there shall be adequate arrangements separated from potentisation chamber for washing, cleaning and drying such containers with suitable equipment for the purpose. Wherever these are attended manually adequate precaution of perfection in respect of cleanliness and avoidance of pollutants shall be taken.
2. Requirements of Plants and Equipments:
(a) Mother tinctures, External tinctures and mother solution section:- The following plant and equipment shall be provided, namely:-
ii) Sieved Separator.
iii) Balances and fluid measures.
iv) Chopping boards and knives.
v) Macerators with lids.
vi) Percolators with and regulated discharge.
vii) Moisture determination apparatus or other suitable arrangement.
viii) Filtering arrangement.
ix) Mixing vessels and suitable non-metallic storage containers.
x) Portable stirrers.
xi) Water still.
1. As far as possible metal contacts may be avoided once the drugs is processed.
2. An area of 55 sq. meters is recommended for basic installations.
3. Adequate separate storage facility should be provided for raw material quarantine, storage and bonded room for alcohol where applicable.
4. Separate and suitable storage facility should be provided for fresh herbs and odorous raw materials.
5. Adequate laboratory facility shall be provided for testing of raw materials and finished products.
(b) Potentisation Section-
(1) The following arrangements are recommended for container for closure preparation section namely:-
i) Washing tanks with suitable brushing arrangement manual or mechanical.
ii) Purified Water rinsing tank.
iii) Closure macerating or washing tanks.
iv) Drying chambers.
An area of 20 sq. metres is recommended for basic installations.
(2) The following arrangements are recommended for potency preparation section namely:-
i) Working tables with washable top.
ii) Facilities for separate storage of different grades of back potencies.
iii) Suitable measuring devices for discharge of drug and diluent in potentisation vial.
iv Potentiser with counter or suitable manual arrangement.
An area of 20 sq. metres is recommended for basic installation.
1. Different droppers shall be used for different drugs potencies.
2. All measuring devices shall be in metric system and be made of glass and shall be free from metallic contents.
3. It is desired that glass droppers etc. intended for re-use after cleaning should be sterilized by autoclave or by heating in a hot air oven.
4. Plastics, rubber tubes, bulks etc. coming in contact with tinctures or back potencies should not be re-used for other tincture and potencies.
5. Method of potentisation will be adopted as specified in Homoeopathic Pharmacopoeia of India Vol. 1 (3) Triturating, Tableting and Pill / Globules section.
The following arrangements are recommended:-
i) Triturating machine of suitable device.
iii) Mass Mixer
vi) Tableting purches or machines
vii) Kettle (Steam / gas / electrically heated) for preparation solution.
ix) Sieved separator, tablet counters and balances.
Tablet section shall be free from dust and floating particles. An area of 55 sq. metres is recommended for basic installations.
4. Ointments and lotion section:
The following arrangements are recommended namely
i) Mixing tank
ii) Kettle (steam, gas or electrically heated)
iii) Suitable powder mixer.
iv) Ointment mill.
v) Filling equipment or arrangement.
An area of 20 sq. metres is recommended for basic installations:-
i) Mixing and storage tank
ii) Portable mixer.
iii) Filtering equipment
iv) Water still/ Deioniser
(Filling and sealing equipment).
An area of 20 sq. metres is recommended for basic installations.
5. Ophthalmic Preparations.
The following equipment is recommended for manufacture under aseptic conditions of Eye-Ointments, Eye-Drops, Eye-lotions and other preparations for external use namely:-
i) Hot air oven electrically heated with thermostatic control.
ii) Colloid mill or ointment mill
iii) Kettle (gas or electrically heated) with suitable mixing arrangement.
iv) Tube filling equipment
v) Mixing and storage tanks of stainless steel or of other suitable material.
vi) Sintered glass funnel seitz filter of filter candle.
vii) Liquid filling equipment
Adequate precaution should be taken to ensure that the finished product is sterile. An area of 20 sq. metre is recommended for basic installations.
6. Adequate arrangements for space and equipment should be made for labelling and packing.
The Drugs and Cosmetics Rules, 1945, as amended upto 1-5-1979 is contained in the publication of the Ministry of Health and Family Welfare (Department of Health) containing the Drugs and Cosmetics Act and the Rules (PDGHS-61). Subsequently the said rules have been amended by the following notifications published in Par II, Section 3 (i) of the Gazette.
GOOD MANUFACTURING PRACTICES
The Homoeopathic Pharmacopoeia Convention of the United States accepts the Current Good Manufacturing Practices for Human and Veterinary Drugs as published in the Federal Register Vol. 43, No. 190, September 29, 1978 and promulgated by the Food and Drug Administration in 21 C.F.R. Part 211. For the convenience of the reader, some of these requirements are summarized below. For full information pertaining to good manufacturing practices, readers should refer to the Code of Federal Regulations a summary of which follows:
I -Organization and Personnel
A. Quality Control Unit
A quality control unit must be established, with the responsibility of approving or rejecting all materials, and the authority to review all production records. Adequate laboratory facilities must be available to the unit. Written procedures detailing the responsibilities of the quality control unit are required.
B. Personnel Qualifications
Employees must be trained in the particular operations they perform, and in good manufacturing practices they relate to the employee’s functions.
Consultants advising on the manufacturing, processing or holding of drug products must have the education, experience or training appropriate to qualify them for the services they perform. Records must be kept of the qualifications of any consultants and the type of services they provide.
II- Building and Facilities
A. Design and Construction Features
The firm’s operations must be performed in specifically or defined areas, to prevent contamination or mixups. )Previous regulations required only adequate space to perform the operations.)
written procedures must be established and followed for sanitation operations. They must include descriptions of cleaning schedules and the methods, equipment, and materials used in cleaning the buildings.
A. Cleaning and Maintenance
Written procedures must be established for equipment and utensil cleaning and maintenance, including a detailed description of methods, equipment and materials used in cleaning and maintenance operations, and of methods of disassembling equipment for cleaning.
Records must be maintained of maintenance, cleaning, sanitizing and inspection of equipment.
B. Automatic, Mechanical and Electronic Equipment
Equipment must be routinely calibrated or inspected, and records maintained. For computer systems, controls must be established to assure that only authorized personnel can institute changes in master production and control records.
Iv- Control of Components and Drug Product Containers and Closures
A. General Requirements
Written procedures must be developed for controlling drug components, containers, and closures, from the time of receipt through handling and testing operations.
B. Receipt and Storage of Untested Components, Containers and Closures.
These items must be stored under quarantine until they have been tested or examined. (The previous regulations required that components be withheld from use until tested.)
Procedures for sampling and testing have been made more specific in the amended regulations. For components, samples must be tested for identify and conformance with written specifications; a report of analysis from the supplier is acceptable in lieu of testing. For containers and closures, tests must be conducted to determine conformance to written procedures; a certificate of testing from the supplier is acceptable in lieu of testing.
C. Containers and Closures
Written procedures must be developed describing standards and specifications and method of testing containers and closures.
V- Production and Process Controls
A. Written Procedures
Procedures must be established in writing for production and process control, to assure that drugs have the correct identity, strength, quality, and purity. Any deviation from these written procedures must be recorded and justified.
B. Calculation of Yield
Yield (both actual and as a percentage of theoretical yield) must be determined at the completion of each appropriate phase of manufacturing, processing, or packaging, or holding of the drug product.
C. Time Limitations on Production
Time limits must be established for the completion of each phase of production, where appropriate, to assure the quality of the drug product.
D. Control of Microbiological Contamination
Written procedures must be established to prevent microbiological contamination of drug products.
A written system must be developed for reprocessing batches which do not conform to standards or specifications. Any reprocessing must be approved by the quality control unit.
VI- Packaging and Labeling Controls
A. Written Procedures and Materials Examination
Procedures must be developed in writing describing the receipt, identification, storage, handling sampling, examination, and testing of labeling and packaging procedures.
Labeling and packaging materials must be examined or tested prior to use.
Records must be maintained for each shipment of labeling and packaging material, indicating receipt, examination or testing, and whether it was accepted or rejected.
B. Labeling Issuance
Procedures must be established to reconcile the quantities of labeling issued. Any discrepancies between the quantity issued and the quantity of drug product finished must be evaluated.
Written procedures must be developed describing the controls employed for the issuance of labeling.
C. Packaging and Labeling Operations
Written procedures must be designed to assure that correct labeling and packaging materials are used for drug products.
D. Drug Product Inspection
Packaged and labeled products must be examined during and at the completion of, finishing operations, and the results must be recorded in the batch production or control records.
E. Expiration Dating
Expiration dating is not required for homoeopathic drugs, or for human OTC drug products if their labeling does not bear dosage limitations and they are stable for at least 3 years. Expiration dating is not required under Section 211. 137 (e). Under Section 211. 166 (c), the stability testing requirements for homoeopathic drugs are satisfied by a written assessment of stability, based on testing or examination of the drug for compatibility of components, and marketing experience indicating there is no degradation over the normal or expected period of use. The stability evaluation should be made using the container system in which the drug is marketed. (See Sections 211. 133 (e) and 211. 166(c).
VII- Holding and Distribution
A. Warehousing Procedures
Procedures must be established in Writing describing the warehousing of drug products, including quarantine of drugs before released by the quality control unit, and storage of drug products.
B. Distribution Procedures
Written procedures must be established describing distribution of drug products, including the practice of distributing the oldest approved stock first.
VIII – Laboratory Controls
A. Stability Testing
A written testing program must be designed to assess the stability characteristics of drug products.
The requirement for testing are listed with more specificity here than in the superceded regulations.
There are different requirements for stability testing of homoeopathic drugs. a written assessment of stability is required based on testing or examination of the drug product for compatibility of the ingredients, and on marketing experience with the drug product to indicate that there is no degradation of the product for the normal or expected period of use.
B. Special Testing Requirements
Written test procedures must be established for sterile and pyrogen-free products, for ophthalmic ointment, and for products in controlled-release dosage form, to determine conformance to specifications.
C. Reserve Samples
If a drug product contains no expiration date, then the reserve samples of the active ingredients used in the lot must be retained for at least 3 years after distribution of the last drug product lot containing the active ingredient. (The previous regulation required samples to be retained for 2 years under these circumstances.)
IX – Records and Reports
A. General Requirements
Production, control, or distribution records, or records of components, containers, closures, and labeling, must be maintained for one year after the expiration date of the batch or, if there is no expiration date, for three years after distribution of the batch.
Records must be available for authorized inspection during the retention period at the establishment where the activity occurred.
There must be written procedures for review of records to evaluate quality standards.
B. Equipment Cleaning and Use Log
A written records must be kept of major equipment cleaning, maintenance, and use.
C. Records for Drug Components, Containers, Closures, and Labeling
Records must be maintained of the following information: the identity and quantity of each shipment of each lot of components, containers closures, and labeling; results of any test or examination conducted an individual inventory record of each component, container and closure; documentation of the examination and review of labeling, and disposition of any rejected items.
D. Master Production and Control Records
Written procedures must be established describing preparation of master production and control records.
E. Production Record Review
All records of drug product production and control must be reviewed and approved by the quality control unit to determine compliance with all procedures before a batch is released or distributed.
F. Laboratory Records
Records should contain complete data from all tests necessary to assure compliance with specifications and standards, including a description of sample and test procedures, and a statement of the test results.
G. Complaint Files
Written procedures must be established describing the handling of all complaints regarding a drug product.
X. Returned and Salvaged Drug Products
Drug products which have been stored improperly cannot be salvaged. Records must be kept indicating the disposition of such drugs.