Assuring quality is important, right from sourcing of raw material to manufacturing and distribution of pharmaceutical products

BY DR. ULHAS GANU

In the 90s, I was associated with a company that had a joint venture with Pharmacia, a multinational brand that marketed textbook brands of anticancer drugs and nutritional supplements. Most anticancer drugs available back then were lyophilised (powder) formulations. The perception is that lyophilised formulations or powders are more stable to atmospheric temperature variations than ready-to-use (RTU) solutions, though a few exceptions may exist. The introduction of RTU Doxorubicin by a new company aroused tremendous interest among oncologists; there was a huge demand for the same due to the convenience in its usage. Belonging to the research field and having handled high-end analytical equipment like the High-Performance Liquid Chromatography (HPLC) myself, I decided to look at the quality and stability of some brands for qualitative purpose, out QUALITY MATTERS Assuring quality is important, right from sourcing of raw material to manufacturing and distribution of pharmaceutical products By dr ulHas ganu of sheer curiosity. Our laboratory analyzed a host of Doxorubicin brands for quality. While most of the brands from MNCs and Indian companies were of standard quality and gave similar HPLC profile for Doxorubicin with no additional unexplainable (impurity) peaks, the new brand with RTU solution had lesser drug content, due to the generation of degradation products, most likely because of wrong storage conditions.

Being ethical, we discussed the findings discreetly with a few oncologists without disclosing the name of the brand, frankly stating that while almost all the brands available in India were quality products irrespective of being international or Indian, only one of them showed a poor 70% assay. To our surprise, a number of oncologists immediately correlated their efficacy observations and named the brand. Since the products were picked up from the market, the company or the brand as such was not at fault at all as the deviation of storage conditions is beyond any company’s control. For stability, the RTU solution of Doxorubicin needed to be stored at 2°C to 8°C while the lyophilised powder is stable up to 25°C. Though storage ‘at room temperature’ is a misnomer in a vast country like India with huge variations in normal temperature, the differential between 8°C for a ready-to-use solution and 25°C for lyophilised formulation gives a tremendous buffer for stability in favor of the lyophilised product. With the prevalent shortage of electricity and load shedding, it was most likely that the product could have been degraded at the selling point. Companies with quality-conscious staff and cold chain facilities are least likely to supply a substandard product. Thus, in the case of sensitive products, the fewer the transit points, the better the product supplied to its consumers.

The company possibly realized the difficulties their brand may face in India and eventually withdrew the liquid formulation. Though the company is not at fault in such instances, the situation prevails and the patient suffers from suboptimal therapy and possibly unknown adverse effects from the degradation of the product. Interestingly, not all products may be more stable because of lyophilised or powder form formulation. Apart from storage temperature, there could be other factors affecting stability. For example, the drug Cisplatin is likely to be more stable as a solution than powder because of the stabilizing effect of chloride ions used in buffering the solution. Thus, while Doxorubicin is more stable as a lyophilised formulation, Cisplatin is better off as a solution. Diluted solutions of Cisplatin for infusion are more stable if made with saline than dextrose, though its short-term effect may be negligible. On the contrary, it is observed that Carboplatin solutions for infusion are more stable if made with dextrose than with saline. The quality-conscious personnel from various departments of the industry play a huge role in product development but improper distribution can wipe out their efforts. Ensuring proper facilities at the storage point and safe transportation of medicines by a good courier is essentially the company’s responsibility. Though retail outlets may be outside its ambit, these factors are worth monitoring for the time and costs involved. It is our responsibility to handle our part well in completing the quality assurance loop, from sourcing and manufacturing to packaging and distribution, until it reaches the end-user