Good manufacturing practice (GMP) is a part of quality control, which ensures that drugs are consistently produced and controlled in such a way that the drugs meet quality standards appropriate to their intended use. GMP comprises a variety of practices that ensure quality of drugs. It also includes:
■ Raw materials quality assurance
■ Record-keeping throughout the manufacturing process
■ Standards for cleanliness and safety
■ Qualifications of manufacturing personnel
■ In-house testing
■ Production and process controls
■ Warehousing and distribution
In 1976, the World Health Organization (WHO) had prepared a draft on GMP. WHO's guideline on GMP has been adopted by pharmaceutical regulators and pharmaceutical industry in over a hundred countries worldwide. WHO also periodically organizes training programmes on GMP for persons associated with pharmaceutical industries in different countries.
The GMP compliance requirements are tough with European Union and US FDA, as compared to that of WHO GMP. Also, the requirements for GMP are tough with countries like Australia, Canada, Japan and Singapore. In the United Kingdom, the Medicines Act (1968) covers most aspects of GMP. The Medicines Act 1968, which is commonly referred to as 'The Orange Guide' because of the colour of its cover, is officially known as 'the rules and guidance for pharmaceutical manufacturers and distributors. Good distribution practices (GDP) is the latest mandatory requirement added to the guidelines of WHO's current good manufacturing practices.
Industry GMP standards
Virtually, every manufacturer adheres to an in-house GMP standard, which varies from producer to producer. In-house GMPs, while often extremely effective, do not provide provisions for quality verification by outside audit. In order to provide such verification, many are now embracing industry-standard GMPs, which are usually subject to an independent outside audit for compliance.
A coalition of industry trade associations - Council for Responsible Nutrition (CRN), National Nutritional Foods Association (NNFA), American Herbal Products Association (AHPA) and Consumer Healthcare Products Association (CHPA) - had developed a draft version of GMPs and submitted to the FDA in 1995. The FDA subsequently published this GMP in 2002.
The NNFA ComPLI Committee, with their advisory board, developed a new GMP to a level deemed to be effective and appropriate. The NNFA GMP Certification Program was tested during 1998 and made effect in 1999. All NNFA supplier members will be required to comply with NNFA's GMP standards. Compliance entitles producers to include NNFA GMP seal in product literature and on labels.
In USA, GMP refers to the good manufacturing practice regulations promulgated by the US FDA under the Federal Food, Drug and Cosmetic Act. These regulations, which have the force of principle investigational medicinal products, should be produced in accordance with the principles and detailed guidelines of GMP for medicinal products.
In most cases, it is left to the manufacturers to determine the best methods to attain quality objectives. In some cases QS regulation does specify the particular type of method to be used, such as written procedures or written instructions. This does not mean that manufacturers cannot vary from the method specified, if the intent of the GMP requirement can be met by another methods like using an engineering drawing plus a model device as manufacturing instructions. Written procedures are not restricted to paper copies and may be filed and distributed by automated data processing equipment.
In mid January 2006, FDA issued a proposed rule exempting investigational drugs and biologics from following current GMP (cGMP) regulations for phase I human clinical trials. FDA proposed a draft to regulate phase I material by relying on the broad applicability of the Food, Drug & Cosmetic Act (which states that drugs not made as per cGMP are adulterated) and the information submitted by sponsors in investigational new drug (IND) applications. Also, FDA issued a brief guidance that included GMP recommendations for phase I (to replace the formal, legal cGMP regulation) trials and a direct final rule to implement this change, provided they receive no significant adverse comment before the close of the comment period.
GMPs and small & mid cap manufacturers
Typically, large manufacturers will have a strict quality control (QC) system maintained by themselves. However, small and mid cap manufacturers often find it difficult to maintain an in-house QC department and opt for a simpler system. Small and medium manufacturers may not need the same amount of documentation that large manufacturers do in order to achieve a state of control. Apart, some of the records maintained to fulfill the GMP requirements for written procedures might not be as long and complex for small manufacturers.
When small and medium scale manufacturers establish a quality system, it should be maintained. Each manufacturer should assure that with growth and process or product changes their quality system is adequate. This assurance is obtained through proper control, day-to-day observance of operations and by periodic audits of quality system. The auditor should first identify the elements of the company's quality system. Next, the audit should determine how well each element is functioning followed by its adequacy with respect to the intent of the device GMP requirements and meeting the company's quality claims.
GMP applicability
The quality-control regulation applies to drugs intended to be commercially distributed for human use unless there is an approved exemption in effect. Contract manufacturers and specification developers shall comply with the sections of quality control regulation that apply to the functions they perform.
Contract test laboratories are considered as an extension of manufacturer's quality system and presently are not routinely scheduled for GMP inspections. The finished device manufacturer shall meet the requirement of the QC regulation and purchasing, when they obtain products or services. Internal test laboratories, however, are part of a corporate manufacturer that provides services to individual corporation factories and should meet GMP requirements.
Regulations in India
The Pharmacy Act, 1948 is meant to regulate the profession of pharmacy in India. The Ministry of Health, together with Drugs Controller General of India (DCGI) and Indian Council for Medical Research (ICMR) has come out with draft guidelines for research in human subjects. These GCP guidelines are essentially based on declaration of Helsinki, WHO guidelines and ICH requirements for good clinical practice. Schedule M of the D&C Act specifies the general and specific requirements for factory premises and materials, plant and equipment and minimum recommended areas for basic installation of certain categories of drugs. The attempt by Government of India to revise the Schedule M is to upgrade standards to meet the 1992 GMP requirements.
Level of GMP penetration
The bulk pharmaceutical manufacturers in India have US FDA validation, which is considered as the strictest validation in the industry. Many companies have been upgrading their facilities to match internationally recognized standards such as GMP requirements and ISO 9002 certifications.
Indian pharmaceutical industry has been nurtured to a large extent by its patent laws, which recognized only process patents. Though India could build a strong base and infrastructure for production of medicines, which is evident from the impressive growth in production of bulk drugs and formulations, it never cared to spend on research and development (R&D). Expenditure on R&D in India is still less than 3 per cent of the industry's turnover. It may be seen that the Indian pharmaceutical industry has been growing at a healthy 16.7 per cent per annum over the past decade. India is able to meet over 70 per cent of its requirement of bulk drugs and 95 per cent of formulations. The industry is well represented in almost all-therapeutic groups.
To compete with bulk manufacturers, the small and mid cap pharma companies in India must adopt GMPs. But, it is difficult to say that how and to what extent they would comply with the GMP norms. Compliance means obedience, while `regulatory compliance' refers to initiatives calculated to appease the regulatory authorities. To confirm compliance with principles of GMP, regular internal audits should be performed in accordance with an approved schedule.
(The author is a specialist in chemicals and pharmaceuticals)