PRODUCT RECALL: A COMMENTARY ON RISING INCIDENCES

There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing related and safety/efficacy related. It is essential to follow all the guidelines related to drug development and manufacturing procedure to minimize drug recall.


INTRODUCTION
The pharmaceutical industry is at an important crossroads in medical innovations, which develop cures for health conditions. Without this industry, many therapies would not be introduced to the market, and many health problems would remain unsolved. The pharmaceutical industry has traditionally been very profitable, and the global market had annual growth prediction of 5 to 8% 1,2 . Yet amidst the massive increase in the field, factors like product returns and recalls are giving the companies new challenges, such as litigation problems, negative publicity, loss of patent protection for many major drugs and widespread efforts to contain drug spending 3 . On the other hand, increased competitiveness, fast-changing structure of competitors, complex strategic positioning, shrinking pipelines, counterfeit drugs and a fight for global market share are adding more burdens to the growth of the industry 4,5 . For a detailed introduction on this topic readers are advised to see the first part of this review 6 . In this previous part published in this journal we have discussed issues like Lack of sterility assurance, Presence of particulate matter and container/closure problems. In this second part, the focus will be on unapproved new drugs, Presence of undeclared therapeutically active moiety, microbial contamination and some other miscellaneous reasons.

ISSUES RELATED TO PRODUCT RECALL I. Unapproved New Drug
The FDA's evidence-based system of drug approval and the OTC monograph system play essential roles in ensuring that drugs are both safe and effective. For instance, during the drug approval process the applicant must demonstrate that its manufacturing processes can reliably produce drug products of expected identity, strength, quality, and purity. The manufacturers of unapproved drug products have not received FDA approval and do not conform to a monograph for making over-the-counter (OTC) drugs. The lack of evidence demonstrating that these unapproved drugs are safe and effective is a significant public health concern (Table 1) 7 . Unapproved drugs are not generic medications, and neither their safety nor their efficacy can be assured 8 . In 2013, retail pharmacies in US filled over three billion prescriptions.   access to timely, accurate and comprehensive information about the medicines they prescribe 9, 10 .

II. Presence of Undeclared Therapeutically Active Moiety
Falsified and substandard drugs may contain toxic ingredients; some of the most compelling stories of pharmaceutical crime are of frank poisoning. By far the more common problem however, is medicine that simply does not work. Medications for chronic and infectious diseases alike have been found falsified and substandard. Data from the FDA office of criminal investigation indicate that pills and tablets are the most commonly compromised products they investigate, mostly produced by individual criminals, not negligent businesses 11 . The WHO is developing a system for the global surveillance and monitoring of falsified and substandard drugs. Different regulatory authorities have different, often widely divergent, requirements.
To complicate the problem, many small regulatory authorities lack the technical depth to evaluate the bioequivalence data generics manufacturers submit ( Table 2) 12 .

III. Microbial Contamination
One of the most important areas in pharmaceutical process control is the development of systems to control the number, survival, and proliferation of microorganisms during manufacturing of non-sterile and sterile pharmaceutical products (Table 3). In relation to this general profile, commonly considered four main sources of microbial contaminations are clean room air, personnel, surfaces and water.
An earlier study, pointed out that maintaining the integrity of a pharmaceutical production environment of clean room is a constant battle 13, 14 . Most common microor-ganisms in clean rooms are gram-positive bacteria. These microorganisms often have a close phylogenetic affiliation as indicated by comparative analysis of partial 16S rDNA studies, such as between the Micrococci and Staphylococci 15 . In addition, there are, in fewer numbers, certain fungi associated with clean rooms. Clean room microflora is predominantly of gram-positive bacteria. With the genera Staphylococcus and Micrococcus, many of the species are indigenous to humans. Although Gram-positive microorganisms are ubiquitous in clean rooms and make up the overwhelming majority of isolates 16 .

IV. Miscellaneous Reasons
The information about counterfeit medicines is everywhere press reports 17 , WHO fact sheets 18 , FDA press releases 19 , U.S. government task forces 20 , law review articles 21 , medical journals 22 and international trade associations 23 . One widely-cited "fact" attributed to the WHO is the claim that counterfeit medicines make up more than 10% of today's global medicines available in the market (Table 4) 24 . Yet another statistic is that in developing countries, up to 25% of the medicines used are counterfeit or substandard 25 . Publicly discussing counterfeiting is an important tool to enforce the industry's price discrimination structures across borders, enhancing overall industry profits 26 .