GMP in Biotechnology products: Dr. Suhasini Bhatnagar

The Indian pharmaceutical Industry, driven by knowledge, skills, low production costs and international quality products has witnessed a robust growth from the production turnover of about Rs. 5000 crores in 1990 to over Rs1 lakh crore in 2009-10 comprising about Rs, 62,055 crores of domestic market and Rs. 42,154 crores of exports. It is, globally, the 3rd largest producer of medicines by volume yet 14th in terms of value.

The lower value is due to the fact that Indian medicines are amongst the lowest priced in the world. However, despite this medicine costs continue to be an important component in the review the situation using insulin as an example-overall medicare expenditure in the country and now being guided by the National Pharmaceuticals Pricing Policy 2012 would be on the basis of regulating the prices of formulations through Market Based Pricing (MBP). On one hand we have the regulations that do not allow the rise in prices and on the other hand we have Biotechnology based techniques and the GMP's that involve a huge amount in terms of necessary infrastructure that add to the cost. So the question is that in products like Insulin while producing it do we need to follow GMP rules strictly, managing a complicated infrastructure and allies necessary.

Let us again review the situation using Insulin as an example. Once a protein's sequence is known, it is possible, in theory, to recreate it synthetically. In fact, insulin was the first protein to be chemically synthesized in a laboratory, in 1963. But researchers were unable to produce much of it. For 60 years after Banting's group isolated insulin, diabetics relied on hormone purified from animals, primarily cattle and pigs. Animal insulin works well on the whole, but is not an exact match with the human hormone and sometimes causes adverse reactions, for example, skin rashes. In 1978 insulin became the first human protein to be manufactured through biotechnology. A team of researchers from the City of Hope National Medical Center and the fledgling biotechnology company Genentech managed to synthesize human insulin in the laboratory using a process that could produce large amounts.

The team inserted the gene for human insulin into bacterial DNA, and used the bacteria as miniature factories to make the A and B chains of the protein separately. In a second step, a chemical process combined them. The result was human insulin, without the problems animal insulin sometimes causes. Humulin, as the commercial product was called, revolutionized diabetes treatment when it became widely available in the early 1980s. Today, almost all diabetic people use recombinant human insulin instead of animal insulin.

With the advent of newer techniques is also another study worth mentioning that of an hormone known as Betatrophin which induces Insulin production by producing more Insulin Producing cells and may be it is possible to take the injection of this Hormone may be once a month or in six months to keep the level of Insulin within limits.

The core set of requirements for GMP would include the procurement of biological starting materials; avoiding contamination of products through facility design, validation and qualification of inherently variable biological processes; stability concerns for labile biological materials; quality control and quality assurance for biological products; risk analysis tools for biological processes; and inspection procedures for manufacturers of biologicals.

The inspectors involved in the Prequalification Programme had identified the need for WHO to start the development of new GMP guidance texts covering:

Microbiological laboratories; and

Computerized systems.

The needs were based on the recommendations made during the forty-first meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations and entire guidelines can be summarized by taking care of 3R’s namely REPLACEMENT, REDUCTION, and REFINEMENT.

The guidance is not primarily about the design of interventions, but about the assessment of interventions in a way that rigorously identifies value for money and supports the development of interventions that provide value for money. The role of this guidance is to supplement the Green Book in the general area of spatially focussed interventions. It should be considered binding best practice in the same sense as the Green Book.

Assessments of spatial interventions will accord with best practice if they are conducted according to the principles of this guidance.

The guidance should not be followed mechanistically, and there may be circumstances when it is right to depart from the guidance.

This guidance pertains to current good manufacturing practice (CGMP) regulations (21 CFR parts 210 and 211) when manufacturing sterile drug and biological products using aseptic processing. Although the focus of this guidance is on CGMPs in 21 CFR 210 and 211, supplementary requirements for biological products are in 21 CFR 600-680. For biological products regulated under 21 CFR parts 600 through 680, §§ 210.2(a) and 211.1(b) provide that where it is impossible to comply with the applicable regulations in both parts 600 through 680 and parts 210 and 211, the regulation specifically applicable to the drug product in question shall supersede the more general regulations.

What can be concluded is that the entire exercise is adding to cost but the benefit is that it will also make the products more and easily acceptable in the world and hence increasing the volume of business that even the small companies can do. Indian companies can very well compete for a market share in other parts of the world as being done for other commodities. So although it increases the cost yet the volume of business shall allow the Indian market to be unaffected and yet do good business outside the country.

"ITS THE VOLUME AND NOT THE WEIGHT THAT MATTERS".