BioTechLogic Attends Society of Chemical Industry (SCI) Analytical Conference in London, November 14th, 2013

Alex Gibb, Manager Analytical Services attended the 2013 Society of Chemical Industry Conference ‘On-Line and At-Line Analytical Technologies in the Industrial Biotechnology Sector’ at the Institute of Practitioners in Advertising in Belgrave Square, London November 14th 2013.

Among the new technologies featured, Optim high throughput analysis and characterization for stability studies from Avacta shows a promising ability to predict activity and aggregation of proteins toward the end of shelf life.  This exciting technology uses a combination of thermal stress and static light scattering that could have applications from clone and media screening to Bioprocess optimization.

SCI, a unique international forum where science and business collide gathered attendees for an interactive session of learning, networking and collaboration.  Hailing from academia and industry, the attendees enjoyed an insightful look into the future of on-line and in-line analytical technologies.

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

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

Alex Gibb Joins BioTechLogic as Manager, Analytical Services

(Glenview, IL) July 9, 2013 –  BioTechLogic, Inc., a biopharmaceutical manufacturing and CMC consulting firm, today announced the addition of Alex Gibb to its growing team of technical experts and consultants.  As Manager, Analytical Services, Gibb will support clients by developing analytical method validation and qualification strategies, preparing method validation and qualification protocols and reports, reviewing internal reports to identify gaps in ICH and regulatory compliance, providing guidance on method requirements and capabilities, providing consultancy on technology transfer, managing third party CRO and CMO testing laboratories, preparing CMC regulatory documentation for IND/BLA/MAA submissions, and performing QC and laboratory audits. Alex was most recently at Novartis Vaccines and Diagnostics in their Analytical Services group, the world’s fifth-largest vaccines manufacturer and the second-largest supplier of influenza vaccines in the United States.

“We’re experiencing a critical time of company growth, and Alex enhances our team’s ability to continue to provide a tremendous breadth of analytical expertise and knowledge,” said Patrick Giljum, Head of Operations, and co-founding Partner of BioTechLogic.

Alex brings over thirteen years experience in the biopharmaceutical industry. In addition to Novartis, he has previously held various positions with Amgen, Sirna Therapeutics and Eltron Research, where he provided analytical technical support; and developed, transferred, qualified and validated methods including UV, HPLC, SDS-PAGE, and MS based methods. Alex has a BSc (Hons) in Ecology with Biology from the University of East Angila, Norwich, United Kingdom.

BioTechLogic has developed proven methodologies and approaches for providing reliable and dependable services to clients in the pharmaceutical industry. For more information about BioTechLogic, visit or call 847-730-3475.

About BioTechLogic

BioTechLogic, Inc., is a biopharmaceutical manufacturing and CMC consulting firm with strategic and practical/hands-on experience that helps clients bring their products to market quickly and successfully by augmenting and optimizing an organization’s technical, manufacturing, analytical, and regulatory resources. The firm offers expertise in process development, BioAnalytical services, process validation, project management, quality assurance, regulatory submissions and Pre-Approval Inspection (PAI) readiness. BioTechLogic’s quality by design (QbD) approach enables the company to effectively provide product development support, including: development reports, design of experiments, technology implementation, critical process parameter evaluation, technology transfer and scale-up, and on-site third party contract manufacturing support.

Global Process Validation Guidance

Medical Device Process Validation

BioTechLogic speaks at 2011 PDA/FDA Process Validation Guidance Workshop


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 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



  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.


  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.