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

uro-med-reg-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
    93/39/EEC,
    93/40/EEC,
    93/41/EEC
    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.

Regulatory

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
http://ec.europa.eu/enterprise/pharmaceuticals/eudralex/vol-10/11_ca_14-2005.pdf

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

Global Good Manufacturing Practices

US GMPS

Background:

References:

EU GMPS

Background:

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

Includes:

ICH GMPs

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)

US BIOLOGIC REGULATIONS

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

BioTechLogic speaks at 2011 PDA/FDA Process Validation Guidance Workshop

BIOTECHLOGIC INVITED TO SPEAK ON PANEL

2011 PDA/FDA Process Validation Guidance Workshop:                    

Aoril 13-14, 2011

JW Marriott San Antonio Hill Country Resort & Spa
San Antonio, TX, USA

Kurtis Epp, Senior Manager, Manufacturing for BioTechLogic, will be presenting during Session P4 – Stage 3 Continuous Process Verification Implementation.  The title of his presentation is “Post Approval Process Validation Reporting.”  He will be available to meet with interested parties during the conference.

The mission of PDA is to advance pharmaceutical and biopharmaceutical technology internationally by promoting scientifically sound and practical technical information and education for industry and regulatory agencies.

BioTechLogic exhibits at IBC’s 13th International Process Validation Exhibition

BIOTECHLOGIC TO EXHIBIT AT IBC’S 13TH INTERNATIONAL PROCESS VALIDATION FOR BIOPHARMACEUTICALS CONFERENCE & EXHIBITION 2009 IN LA COSTA, CALIFORNIA (12/18/2008)

BioTechLogic will be exhibiting at IBC’s 13th International Process Validation for BioPharmaceuticals Conference & Exhibition 2009 in La Costa, California.  The conference, which runs from March 2-3, is co-located with the Outsourcing Manufacturing of Biopharmaceuticals and the Technology Transfer for Biopharmaceuticals conferences.

Exhibiting at the Process Validation conference will provide additional opportunities for continued growth in BioTechLogic’s technical offerings.

“We look forward to the opportunity to showcase our capabilities to a wider audience with bioprocessing needs.” – Peter Dellva, Head of Business and Finance.

 

Brief from PDA workshop on FDA Guidance for Process Validation

BRIEF FROM THE PDA WORKSHOP ON FDA’S NEW GUIDANCE ON PROCESS VALIDATION “THE SHIFTING PARADIGM IN PROCESS VALIDATION” OCTOBER 26-27, 2009 (10/31/2009)

Background:

  1. The FDA’s Draft Guidance on Process Validation is nearing approval stage.  It has been circulating within the industry for comments for a year and FDA is committed to finalizing by the end of 2009.
  2. This was the fourth of five workshops to discuss the new guidance document and to solicit feedback from the industry.  Consequently, the focus of discussions at the PDA workshops has shifted over the course of the year from review to implementation.

Introduction:

  1. The concepts contained in the draft guidance document are not revolutionary.  In many ways, they reinforce what we (BioTechLogic) are already doing.
  2. What we sense as different is a renewed focus on Stage 1 (Process Design) and Stage 3 (Continued Process Verification) during PAI and CMC review.
  3. While we already knew this, “Process Validation” is now being considered as a progressive sequence of activities rather than as an event.  Three consecutive successful full-scale batches is now a minimalistic approach.

Stage 1 (Process Design):

  1. Design of Experiment (DOE) during process development is now a must.  Single variable experiments that lack an evaluation of interacting parameters are not sufficient for gaining process knowledge and defining Critical Operating Parameters.
  2. Process Characterization Reports should include a full discussion of both “design space” and interacting parameters.  Statistical evaluation of experimental data is crucial.

Stage 2 (Process Qualification):

  1. Overall, this stage is very much the same.  The biggest change is that FDA is very hesitant to use the term “three consecutive batches” to describe Process Qualification (PQ).  “As many as it takes to demonstrate process control” is the new mantra.
  2. Additional sampling throughout PQ was emphasized.  It was also noted that additional sampling should continue after PQ and into Continued Process Verification (CPV) until the appropriate process knowledge is gained.

Stage 3 (Continued Process Verification):

  1. There is a strong emphasis on Statistical Process Control (SPC) for this stage.
  2. Whereas commercial data evaluation in the form of an annual report was previously expected, more frequent monitoring and formal internal reporting will be expected.
  3. Investigators are now being trained to inspect commercial sites one to two years post-approval to specifically evaluate: (1) maintenance of a validated process (i.e., CPV), (2) stability data, and (3) quality of incoming materials and components.
  4. The agency strongly recommends a formal protocol for CPV.

BioTechLogic participates on Bio Program Committee

JULIE TRAJKOSKI, SENIOR MANAGER OF OPERATIONS, FOR BIOTECHLOGIC, INC. INVITED TO PARTICIPATE ON THE 2010/2011 BIO PROGRAM COMMITTEE(8/24/2009)

Julie Trajkoski, Senior Manager, Operations for BioTechLogic, Inc. has been invited to participate on the 2010/2011 BIO International Convention Program Committee. The 2010 BIO International convention will be held in Chicago’s McCormick Place Convention Center on May 3-6, 2010.

The world’s premiere biotechnology event, and the industry’s largest and most diverse meeting was held this year in Atlanta, GA, attracted 14,352 attendees from over 60 nations. The exhibition at 2009 BIO featured more than 1,800 companies, organizations, and institutions representing every aspect of the biotechnology industry.

The task of the Program Committee is to help create a top-quality educational convention program by providing expert recommendations to the BIO. There are approximately 17 tracks to be reviewed and the committee members will be tasked to identify the most qualified submissions received. Membership will be made up of local, regional, national, and international biotechnology professionals and members are invited to serve for 2 years to add more continuity to this important role.

BioTechLogic at BioPharm America in San Francisco

BIOTECHLOGIC HEADS TO BIOPHARM AMERICA IN SAN FRANCISCO CA, SEPT. 16TH – 18TH (8/19/2009)

Are you heading to BioPharm America? Partnering has opened and we want to hear from you. BioTechLogic, Inc. is a technology and manufacturing management firm that helps clients bring biopharmaceutical products to market quickly and successfully-by augmenting and optimizing an organization’s technical resources. We understand the difficulties of the drug development process and that even successful biopharma companies are constantly troubleshooting potential roadblocks or are in need of extra manpower to meet timelines or milestones. We can do this and much more. As a proven biopharmaceutical consulting/hands-on resource firm, our expert staff of CMC, Manufacturing, Technology, Analytical, QA [Process and Facility PAI Readiness] and Project Management professionals has helped both oligonucleotide and protein products gain worldwide regulatory approvals.

We’ll be taking meetings all through show hours but if you can’t meet us then or think you will need some dedicated time just give us a call and we’ll set up a meeting. Even if you just want to say hello to the BTL team, make sure to reach out and let us know you are there. See you then!
http://www.biotechlogic.com

Contact:

Peter Dellva
Head of Business and Finance
Phone: 847.730.3475
Email: pdellva@biotechlogic.com