Annual Industry Report

Transcription

1 Annual Industry Report Industry Expert Panel Submissions

2 PANEL MEMBER Dilip Shah, CEO, Vision Consulting Group Drug Regulatory Scrutiny & the Pharmaceutical Industry Summary of Market Predictions of safety and quality the last three years indicates that while many instances of landscape and meet requirements comprehensive over the next five years and safety standards awareness and inadequate appreciation of these continually

3 How Many, and For What? Table 1 Warning Letters by Office of Manufacturing & Product Quality, US FDA No Issue * Total A Active Pharmaceutical Ingredients (APIs) 1 Mfg facility inspection Deviations from cgmp Change notification Total APIs B Finished Pharmaceuticals (Formulations) 1 Mfg facility inspection Violations of cgmp (a) 43 Total Formulations Total API + Formulations Source: (a) Includes API Mfg Facility Inspection of one Unit * To 30 June Only to formulations have increased. It is evident from these Table 2 Warning Letters by Office of Drug Security, Integrity & Recalls, US FDA No Issue * Total 1 Internet Marketing of Unapproved and Misbranded Drugs Source: * Up to 30 June Only

4 Survey Suggests a Need for Greater Control Table 3 of Formulation & Ingredient Management Drug Recalls, Market Withdrawals & Safety Alerts by Reason, US FDA CPhI s first survey on formulation suggests that drugmakers No Reason/Problem * Total % of Total 1 Undeclared ingredient; including sildenafil, communicate more closely with suppliers, and better acetaminophen, dexamethasone, diclofenac, etc. understand and control their processes 2 Visible particulates; including fungal microbial contaminants, precipitation/crystallization, brass particulates, etc. Introduction 3 Unapproved drugs Sterility Few 5 would Deviations dispute in fill the volume, fact that pharmaceutical 0 3 formulation 7 1 has 11 pharmaceutical 6.2 value chain. The unit operations that precede become Size/Thickness increasingly of challenging. Tabs, variations The difficulties all start with formulation can be extremely difficult to control. in tablet strength, etc. the 6 ingredients Packaging error; used including to make finished 0 drugs. 6 As more 3 Active Pharmaceutical mislabeled/incorrectly Ingredient labeled (API) and excipient manufacturing In addition, many developmental products now in the pipeline bottles, and bottles containing moves wrong offshore, drugs, particularly etc. to India and China, there have been are insoluble or difficult to work with. The Venus de Milo is 10 increasing 7 Quality complaints control and of variable quality 1 and 1 tightening 0 supply. 1 3 times 1.7 more soluble in water than many APIs, noted Shaukat manufacturing processes, insufficiencies in the Ingredients development have never of the officially been covered by existing manufacturing process or noncompliance with drug pharmaceutical good manufacturing practices (GMPs), although manufacturing different requirements countries follow guidelines set by WHO, Ali, technical sales manager of BASF s Pharma Ingredients and Services at a Catalent Applied Drug Delivery Institute training event on June 12. as 8 well Equipment as ICH Q7. cleaning, leading to He said 1.1 that most APIs now commercially available are insoluble, product containing trace amounts of other drugs as well as the growing number of t in the pipeline. What Supply 9 Others; chain including disasters contamination, of 2008, the heparin 0 18 recalls 13 and 7 38 cannot 21.3 be dissolved cannot be absorbed, and cannot cure. odour, impurity, leaking tainted container, glycerin difficulty tragedies, in using focused attention on the lack of Click here for an article on absorption modeling. systematic measure and dosing harmonized system, etc. global quality control standards for Total pharmaceutical ingredients CPhI and CPhI PharmaEvolution.com surveyed readers on their Source: * Up to 30 June 2013 experiences and challenges in formulation and ingredients sourcing and management. Responses from 123 industry professionals suggest main areas of concern and overall trends. Sweeping regulations in Europe and the US, namely the Falsified Medicines Directive and the FDA Safety and Innovation Act, aim to address this need, and improve the safety and quality of APIs and ingredients. Globalization of the market has Table also heightened 4 awareness that Drug the Recalls, world s Market regulators Withdrawals couldn t & Safety possibly Alerts inspect by Company, every US FDA pharmaceutical No Frequency ingredients 2010 plant 2011 or 2012 all the 2013* new API Total and % of Total ingredient 1 1 Time manufacturing 17 facilities 24 coming 30 online. 25 Regulatory authorities, 2 2 Times including EMA 1 and 4 FDA, 3 collaborated 6 on 14 some API 12 plant 3 inspections, 3 Times and have recognized 2 1 a role 1 for independent 4 3 third-party 4 4 Times auditors for 1 API and ingredients 1 facilities Times This 6 has > 5 led Times to the development 2 of formal 1 cgmp guidelines 3 for 2 India The Main Source Of APIs And Ingredients Total excipients and new options such as third-party supplier auditing and qualification programs. But formulation challenges continue, all along the Brian Carlin, Director, Open Innovation, at FMC BioPolymer, an expert in excipients; Girish Malhotra, President of Epcot International, an API expert, and Emil Ciurczak, independent NIR spectroscopist and PAT expert; all on CPhI s Advisory Board; and Irwin Silverstein, VP and COO of IPEA, commented on the overall results, which are summarized in this brief report. IPEA was the first third-party excipient auditing organization, which, together with the Pharmaceutical Quality Group, drafted the cgmp requirements for excipient suppliers. On the ingredients sourcing side, survey respondents say they are getting most of their APIs and ingredients from India, and, when they partner or outsource any activities, they are

5 Not Learning from Mistakes one violation. Also of concern is the types of default that are on the rise. industry. It is noteworthy that these incidents declined and quality medicines. Attempts to Beat the System Cultural Change And Communication wide. It is a slow process that will require patience and 11

6 make more effort to communicate the rationale of the Barriers to Market Entry which will ultimately reduce competition. Another point to consider is the need for and likelihood of thus likely that the industry will have to continue to have to will push up the price of medicines as companies face competition. What s the Solution? auditors can only expose technical deficiencies and help implementation of processes that could address causative 12