Evolution of Good Manufacturing Practices
H B Dandekar
Good Manufacturing Practices (GMP) in the manufacturing of pharmaceuticals are those practices which ensure the continuous manufacturing of pharmaceuticals, having previously laid down quality parameters.
The evolution of GMP in pharmaceutical manufacturing may be traced back to the year 1960/61, when entire Europe was shaken by the birth of over 10,000 deformed babies by women who had consumed a tranquiliser drug ‘thalidomide’ during the period of their pregnancy. The problem was further compounded when the progeny of some of the deformed (Thalidomide babies) persons was also born deformed. The obvious reason of this major tragedy was either the absence or negligence of a study of proper effects of the new drug on the next generation.
In India, pharma industry started in around 1900 and was mainly focused on formulations. The Drugs and Cosmetics Acts and Rules were brought into effect in 1945. Till the 1970s, the Indian pharma industry was mostly manufacturing formulations with very few bulk drug/active pharma ingredients. Though, by and large, the quality was genuinely maintained, there was no concept of quality assurance. The terms GMP, documentation, SOPs, BMR validation, qualification, internal audit, training, were unheard of. There used to be only quality control. After 1975, there was a major growth in the industry when many Indian pharma companies entered into bulk drug manufacturing, hence, entering the international market. Naturally, they had to follow the stringent quality requirements of World Health Organization (WHO); thus, there was a gradual introduction of GMP through WHO’s international quality requirement.
In 1986, a number of patients in one of Mumbai’s leading hospitals died of poisoning due to usage of adulterated glycerol. The toxic adulterant found was diethyl glycol. An enquiry committee under the chairmanship of late Justice Lentin brought the people concerned to the task. During a raid on the premises of a scrap dealer in 1992, many rejected labels and cartons in bulk of pharma formulations of a leading multinational pharma companies were found. On interrogation, the scrap dealer confessed to selling these rejected packing materials to a small manufacturer making spurious drugs.
In 1996, one of the brands of the product Co-trimoxazole of a leading multinational pharma company was found to contain an antidiabetes drug—glibenclamide—as a result of a mix up while manufacturing. This resulted in a sudden and drastic rise in blood sugar level and blood pressure of several patterns and many of the affected people were critical after consuming those tablets in an eye camp. The Managing Director of the company left India for Canada.
These are some of the known and major cases found to be violating fundamental quality practices. There may be many unknown cases as well, but all these incidences must have led to many positive changes in the Drugs and Cosmetics Acts, 1941:
1. Around the year 2000, introduction of revised Schedule M gave in detail the requirements as per GMP for the premises and equipments for manufacturing of pharmaceuticals
2. Schedule T introduced GMP requirement of plant and equipment for ayurvedic and unani pharma products
3. Schedule U stated that particulars required to be shown in manufacturing of pharmaceuticals in their records
4. Schedule V introduced the standards of patents and proprietary medicines, and declared therapeutic and prophylactic dosages for certain drugs/vitamins.
The WHO requirement for registration of products for export was still stricter, where a company had to make and submit site master files giving the details of itself and its quality systems, documentation, validation, self inspection/internal audit etc.
The quality requirement in regulatory authorities of developed nations is still more stringent, as filing drug master files and giving exhaustive details of the product manufactured and intended to be exported is a necessity.
Schedule M of Drugs and Cosmetic Acts 1940 regarding GMP and requirements of premises, plants and equipment for manufacturing of pharmaceutical products is quite exhaustive . It covers many aspects eg general requirements, locations/surrounding, building/premises, water system, warehousing area, production area, ancillary area, quality control area, personnel, health, clothing and sanitation, manufacturing, operations and controls, sanitation of manufacturing premises, raw materials, equipment, documentation and records, labels and other printed material, quality assurance, self inspection and quality audit, quality control system, specifications, master formula record, packaging records, batch packaging record, batch processing record, standard operating procedures and records, reference samples, reprocessing and recoveries, distribution records, validation and process validation, product recalls, complains and adverse reactions, and site master file.
The Indian pharma industry is growing at the rate of 10 percent as against the global growth of seven percent. At the same time, the menace of spurious drugs is also increasing at an alarming rate, not to forget the competition from countries like China. All this makes it very essential to not only introduce, but also inculcate the system of GMP. The initial investment cost will be there, but on successful implementation and follow up of GMP the advantages are many e.g. Increase in productivity, reduction in wastages, increase in yield, high moral of staff/work, better working condition, better image of the company.
While introducing GMP it is advisable to do first cost benefit ration of the investment versus returns, plan the products to be manufactured; understand and correctly implement the FDA GMP guideline, take the guidance and advice from the proper people who are experts in the field, appoint qualified and experienced staff to carry out different activities. Finally, GMP should be taken as an attitude. It is an investment which, if made properly, will yield good results tomorrow.
(The author is associated with Umang Pharmatech, Email: email@example.com)