Introduction and Overview

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Pharmaceutical Industry

• Introduction and Overview

PRA700
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Major Players

• General public
• Pharmaceutical Companies
• Physicians
• Pharmacists
• Governments

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Pharmaceutical Companies

• Innovator
• Generic
• Third Party
• Ultra Generic

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Innovator Companies

• original research
• new molecules as the starting point for
  innovative drugs (synthesis or isolation)
• Preclinical studies
• chemistry
• physical aspects of the molecule

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Innovator Companies (continued)

• Biological aspects of the molecule
• a) pharmacology, ADME i.e., absorption,
  distribution, metabolism and excretion
• b) Toxicological properties of the new molecular
  entity
• Formulation trials
• biologically active molecule is processed along
  with pharmaceutical inactive ingredients to
  produce pharmaceutical dosage forms

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Innovator Companies (continued)

• Clinical studies
• Phase 1 Introduction of investigational drugs
  into humans for the primary purpose of assessing
  safety and establishing tolerant dose.
• Phase 2 Establishing the efficacy of the drug
  by using a small number of patients.
• Phase 3 Establishing the efficacy, safety and
  all other aspects of the drug by using a thousand
  or more patients.

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Innovator Companies (continued)

• They are the first to make scientific
  submissions.
• submit Clinical Trial Application (CTAs) to the
  Regulatory Authorities.
• Conduct ongoing Clinical Trials.

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Innovator Companies (continued)

• In summary the innovators are the first
  pharmaceutical companies to establish the drug
  product on the market and promote its
  effectiveness to physicians thereby establishing
  demand for the drug.
• Examples of Innovator Companies GlaxoSmithKline,
  Novartis (Ciba-Geigy and Sandoz), Wyeth-Ayerst,
  Merck, Bayer, Eli Lilly.

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Generic Pharmaceutical Companies

• inexpensive (or less expensive) copies of the
  innovators' product
• scientific submissions to Regulatory Authorities
• abbreviated compared to the innovators
• Abbreviated New Drug Submissions (ANDS) submitted
  to Regulatory Authorities

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Generic Pharmaceutical Companies (continued)

• CTAs are submitted but adherence to the
  guidelines differs from the innovative companies
• Not required to conduct phase I, II and III
  clinical trials
  
  
  

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Generic Pharmaceutical Companies (continued)

• required to formulate the product
• approval to market a copy of an innovator's
  product involves demonstration that their copy is
  equivalent in terms of safety, efficacy and
  quality to the innovator's product
• bioequivalency is demonstrated through a series
  of chemical and physical laboratory tests

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Generic Pharmaceutical Companies (continued)

• Examples of Generic Companies
• Apotex, Novex Pharma, Torpharm
• Novopharm
• Genpharm Inc.

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Third Party Pharmaceutical Companies

• Contract laboratories
• Raw material distributors
• Consultants
• participate in part of the process of drug
  development
• conduct bioequivalence studies

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Third Party Pharmaceutical Companies

• Examples of Third Party Pharmaceutical Companies
  Patheon, Roberts Pharmaceuticals, Global, PDi,
  Biovail, Phoenix, CanReg, CanTox Inc.

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Ultra Generic Pharmaceutical Companies

• Market a product that is manufactured by
  innovator companies
• Minimal research and development
• Reference to innovators approval by regulatory
  body
• Also called Super Generic
• began 1997
• Example of Ultra Generic AltiMed

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Departments within a Pharmaceutical Company

• Marketing/Sales Department
• Product selection criteria
• sales volume b
• potential sales volume based on the number of
  people who are afflicted by a particular disease
  for which the drug product is designed to relieve
  (innovators)
• level of difficulty involved in the processing or
  product formulation

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Departments (continued)

• availability of adequate amounts of raw material
• product exclusivity/patent protection
• therapeutic niches

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Departments (continued)

• Formulation or Product Development Department
• Pre-formulation dosage strength, dosage form,
  development and manufacturing process
• Formulation direct compression, dry granulation,
  wet granulation

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Departments (continued)

• Stability Testing (or New Product Testing)
  Laboratory
• before being approved for distribution and sale a
  product must be tested for stability
• stability of the drug refers to its ability to
  maintain its physical, chemical (and
  microbiological for drugs other than solid
  dosage forms) integrity or wholesomeness over a
  period.

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Departments (continued)

• stability testing provides the following
  information
• stability of drug substance in the presence of
  light, heat, moisture, packaging, excipients,
  etc.
• storage conditions (including packaging material)
• duration of formulation stability
• product expiry dates

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Departments (continued)

• Bio-analytical Laboratory (Biolab)
• innovator and generic drugs require different
  levels of bioanalytical testing of the drug
  product.
• All tests conducted on analytes (drug substances,
  metabolites, impurities, etc.) in the biological
  system (i.e., blood, urine, etc.) are performed
  by the Bio-analytical Laboratory.

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Departments (continued)

• Innovator drug plasma concentration of the drug
  related to clinical response (i.e., the
  therapeutic and adverse effect of the drug on a
  healthy or subject patient)
• innovator is also expected measure the impurity
  (including metabolites) plasma concentration to
  assess their toxicological impact on the study
  subject

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Departments (continued)

• Generics required to demonstrate bioequivalency
  of their product when compared with the innovator
  product

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Departments (continued)

• Manufacturing
• unlike the Formulation or Product/Process
  Development Departments which are working with
  small scale trial batches, Manufacturing deals
  with the routine production of large scale
  (usually in excess of 100,000 tablets)
  pharmaceutical products

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Departments (continued)

• Quality Control Department
• During manufacturing it is imperative that
  physical and chemical (also microbiological for
  liquids, semisolids and preservatives) testing be
  continued, on a regular basis, to monitor the
  quality of the drug product
• This is achieved by the Quality Control (QC)
  Department using physical and chemical methods
  (stability-indicating methods)

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Departments (continued)

• Quality Assurance
• responsible for documentation
• involved in inspections by regulatory bodies

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Role of Regulatory Affairs in Pharmaceutical
Industry

• Regulatory Affairs Department
• Pharmaceutical companies are required to submit
  scientific data regarding their product to
  Regulatory Authorities
• Examples of Canadian submissions are Clinical
  Trial Application (CTA), New Drug Submission
  (NDS), Abbreviated New Drug Submission (ANDS),
  Supplemental New Drug Submission (SNDS) and
  Abbreviated Supplemental New Drug Submission
  (ASNDS)

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Role of Regulatory Affairs in Pharmaceutical
Industry

• Regulatory Affairs is the department of a
  Pharmaceutical company that deals with all
  aspects relating to the submission
• collect scientific data from the many labs
• collate this information onto the submission
  forms provided by the regulatory body

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Role of Regulatory Affairs in Pharmaceutical
Industry

• RA receive the letters of approval (called Notice
  of Compliance) from the regulatory body giving
  permission to sell its product
• RA is the department that may receive letters of
  non-approval (NON) which means the contents of
  the submission are not sufficient to support
  approval of the drug product
• Clarifaxes NOD are also received by RA to
  address issues in the submission

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Role of Regulatory Affairs in Pharmaceutical
Industry

• RA personnel are at the forefront of regulatory
  issues they inform the rest of the company about
  any new Good Manufacturing Practice (GMP)
  requirements
• RA can therefore be viewed as a facilitator they
  facilitate communications between the many
  pharmaceutical departments and the regulatory
  bodies

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Summary

• Large industry
• Extensive documentation
• Many opportunities