White Papers, Executive Briefs & Slideshares

The Evolution of Therapeutic Monoclonal Antibodies (mAbs)

Enabling technologies are tackling development and manufacturing challenges, paving the way for dynamic mAb innovations. Download white paper


Key Considerations in Gene Therapy ManufacturingeBook: Key Considerations in Gene Therapy Manufacturing for Commercialization

Compiled by 13 collaborators, this piece looks at the future of gene therapy commercialization including: the regulatory landscape, upstream and downstream manufacturing, analytical approaches and much more. Download eBook


Oligonucleotides: Opportunities, Pipeline and Challenges

Oligonucleotides: Opportunities, Pipeline and Challenges

Although meaningful progress toward the development of oligonucleotide therapeutics began in the 1970s, nearly a half century later, only six oligonucleotide drugs have been approved by the FDA as of November 2017. However, the field is gaining momentum and the clinical benefits of the dozens of oligonucleotide therapeutics currently in various stages of clinical trials are extremely promising.

This paper discusses the challenges, as well as the technologies helping to overcome the challenges, of commercializing oligonucleotide therapeutics. Also included is a Q&A with Tracy TreDenick, Head of Regulatory and Quality Assurance for BioTechLogic. In this Q&A she discusses BioTechLogic’s firsthand experience and perspectives on commercializing oligonucleotide therapies. Download paper


Gene Therapy CMC ThumbnailGene Therapy CMC Strategies Paving the Way for Commercialization

While significant advancements have been made, gene therapies still present many manufacturing challenges, this paper explores CMC approaches gene therapy developers are applying to increase success rates. Download paper


4 SteBiopharmaceutical Project Management Thumbnailps for Managing the Criticality and Challenges of Biopharmaceutical Projects

Biopharmaceutical project management is exceptionally challenging, requiring unique experience and expertise. This paper explores the demands of the field and insights for managing them. Download paper


 Expedited Approval Drug White Paper ThumbnailProcess Validation and Regulatory Review in the Age of Expedited Approval Drugs

Expedited approval drugs have profoundly changed the thinking and approach to Process Validation and other CMC activities. When working on the development of an expedited approval drug, Chemistry, Manufacturing and Controls (CMC) data needs to be generated in about half the time of the traditional process. Of course, an expedited approval classification does not mean that the drug developer can do less. In order to meet these accelerated timelines, analytical methods creation and product and process characterization needs to start sooner, and the process needs to be handled differently. This paper explores those dynamics and offers some revised approach suggestions. Download paper


Combination Products Paper Thumbnail4 Things You Need to Know About Combination Drug Compliance

Combination products are a fascinating area of the pharmaceutical industry and present great future promise. The segment is projected to reach $115 billion in global sales by the end of 2019. It has grown solidly at a rate of 7.9% CAGR since 2013, and is projected to continue at that rate through 2019.1

Some of the key factors driving this growth include: higher levels of patient compliance, demand for minimally invasive surgeries, opportunities for precise pain relief, quicker healing and governments and non-governmental organizations (NGO) embracing combination drugs for their ease of administration.

However, combination drugs present unique challenges addressed in this paper:

  • What is 21 CFR Part 4?
  • Understanding the Role of the FDA’s Office of Combination Products
  • Bringing Legacy Combination Products into Compliance with 21 CFR Part 4
  • Streamlined Approach for Review and Approval of Some Combination Products

Download paper


EU Regulatory References

1. EU Regulations

EMEA Biologics

The European Commission (formally the Commission of the European Communities) is the executive branch of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union’s treaties and the general day-to-day running of the Union. The European System is based on the cooperation between the National Competent Authorities of the member states and the EMA (European Medicines Agency).

European Medicines Agency, EMA

  • The EMA is headed by the Executive Director and has a secretariat of about 440 staff members in 2007. The Management Board is the supervisory body of the EMA, responsible, in particular, for budgetary matters.
  • Responsible in EU for coordinating:
    1. Scientific resources provided by Member States for the evaluation, maintenance and pharmacovigilance of medicinal products.
    2. The Court of Justice of the European Communities exercises jurisdiction over the EMA for the application of Community Law.

The European Pharmaceutical Regulatory System is based on complementary procedure for the registration of medicinal products:

  1. Centralized Procedure: mandatory for biotech-derived medicinal products and optional for other innovative products. This results in a single marketing authorization valid throughout the EU.
  2. Mutual Recognition Procedure: The main route for non-biotech products. Establish a MA in one member state applies for other member states to recognize.
  3. National Procedure: used to authorize medicinal products for local use only

EU – Regulatory Process

  • National authorities / experts – assessment
  • CHMP provided / adopts scientific opinion
    (CHMP composed of Rapporteurs – representing National Authorities)
  • European Commision – legislative decision
  • Centralised Authorisation – valid for all (25) Member States (~450 million people).

European Medicines Regulatory History


Europe’s Pharmaceutical Legislation

  • 1965: Dir 65/65/EEC : Safeguard public health after Thalidamide; a highly sophisticated system of legal provisions dealing with medicinal products.
  • 1975: Dir 75/318/EEC: Establish Laws in Member States relating to Analytical, pharmacotoxicology, and clinical standards (quality, safety, and efficacy)
  • 1975: Dir 75/319/EEC: Established CPMP to ensure companies comply with former directive and introduce concept of mutual recognition [established as a scientific review committee]
  • 1987: Dir 87/ 22 EEC: Requirements for approval of “High Technology” Medicinal Products particularly those derived from Biotechnology
  • 1983: introduction of the mutual recognition process in 1983 (established as anamendment to directive 75/319)(1), made it possible for a single national review for most pharmaceutical/medicinal products to be used as the basis for marketing authorizations in all EU countries.
  • 1991: Dir 91/356/EEC: Principles of GMP’s for human products
  • 1993: 3 Directives and a regulation together form the legal basis for the EMEA system
    Regulation (EEC) No 2309/93.
    The centralized procedures for authorizing biotechnology -derived and high technology Medicines is laid down in Council Regulation (EEC) No 2309/936 and Directive 93/41/EEC.
  • 1995: Council Regulation EEC 2309/93 ; Creation of EMEA and unification of regulatory process (creation of centralized procedure)
  • The current relevant legislation is given in Directive 2001/83/EC relating to medicinal products for human use, amended by Directives 2002/98/EC, 2003/63/EC, 2004/24/EC and 2004/27/EC.


EMA’s Regulatory Pathway

  • The application is submitted directly to the EMA in London.
  • At the conclusion of the Scientific Evaluation (210 days) at the Agency, the opinion of the Scientific committee is transmitted to the Commission for single Marketing Authorization applying to the entire EU (all member states).
    EMEA Chart
  • 2001, European Parliament and the Council adopted Directive 2001/83/EC on the Community Code relating to medicinal products for human use. The so-called “Community Code Directive” combined in one legal act nearly all aspects of European law on medicinal products.
  • The European Community revised two legislative acts: Directive 2001/83/EC on products subject to national authorisation and mutual recognition was amended by new Directive 2004/27/EC (“Revised Community Code Directive”) and the former Regulation 2309/93/EEC of 22 July 1993 on centrally authorised product was replaced by Regulation 726/2004/EC (“Revised Community Procedures Regulation”).
  • In addition several other laws were issued, such as Directive 2002/98/EC (re human blood) and Directive 2003/63/EC (re dossier harmonisation) as well as Commission Regulations (EC) 1084/2004 and (EC) 1085/2003 (re variations) and directives dealing with human tissues and herbal medicinal products.

EU Submission Requirements

Phase Submission
Clinical Clinical Trial Authorisation (CTA) DIRECTIVE 2001/20/EC (1)
CommercialAuthorization Marketing Authorization Application in CTD Format:Directive 2001/83/EC:• Article 8(3) – Full application• Article 10 – Generic, hybrid or similar biological application• Article 10a – Well-established use application• Article 10b – Fixed combination application• Article 10c – Informed consent application
Post Approval Variations (2)

(1) The Directive 2001/20/EC, the Directive, should be read in conjunction with this detailed guidance, Commission Directive 2005/28/EC2

(2) Variations http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-2/a/v2a_chap5_r1_2004-02.pdf

Global Good Manufacturing Practices






EUDRALEX: Volume 4–Medicinal Products for Human and Veterinary Use: Good Manufacturing Practice



World Health Organization (WHO) GMPs

IPEQ [The International Pharmaceutical Excipients Council]

US Regulatory References

FDA – U.S. Food and Drug Administration

Guidance, Complaince: Regulatory Information (Biologics)


The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the Code Of Federal Regulations (CFR). The CFR is divided into 50 titles that represent broad areas subject to Federal regulations. The FDA’s portion of the CFR interprets the Federal Food, Drug and Cosmetic Act and related statutes. Section 21 of the CFR contains most regulations pertaining to food and drugs. The regulations document all actions of all drug sponsors that are required under Federal law.

Guidance Documents & Links

Global Process Validation Guidance

Medical Device Process Validation