Computers, regulations and long time relationships

1
Computers, regulations and long time relationships

• Hasse Greiner
• Novo Nordisk A/S
• Computer Related Systems Quality

2
Novo NordiskGeneral information

• Headquarters Denmark
• International Production facilities in six
  countries, affiliates or offices in 68 countries
• Workforce18,756 employees (Dec 2003)
• Approximately 60 of employees are located in
  Denmark, 40 in the rest of the world

3
Product Range

• Novo Nordisk has the broadest diabetes product
  portfolio in the industry. We also have a leading
  position in areas such as haemostasis management,
  growth disorders and hormone replacement therapy.

4
The speaker

• Electronics engineer, 1976
• Plant automation, 1976
• programming
• project manager
• System validation since 1988
• Corporate system QA and validation, 1995
• corporate procedures
• audits
• reviews and approvals
• support and training
• inspection support

5
Operational Environment

• The pharma industry is regulated and Novo
  Nordisk is part of it

6
Regulations

• A regulation (as a legal term) is a rule created
  by an administrative agency or body that
  interprets the statute(s) setting out the
  agency's purpose and powers, or the circumstances
  of applying the statute.

7
Developments of Regulations

• Food and Drug Act of 1906 was passed.
• Reason Disclosure of unsanitary meat processing

False therapeutic claims for patent medicines
were basically unregulated, as the manufacturer
had only to show that he personally believed that
his remedy worked to avoid prosecution
8
Development of Regulations

• The need for regulations has stepped up with each
  historical crisis
• 1938 Dr. Massengills Elixir Sulfanilamid,
  causing 107deaths
• 1940 Winthrop Chemical Companys sulfathiazole
  tablets contaminated with Phenobarbital causing
  over 300 deaths.
• 1962 Thalidomide. US narrowly avoided the
  tragedy but Europe and Canada was hurt by over
  10.000 cases of severe deformities.

9
Development of Regulations

• 1973 Drug cGMPs were introduced
• 1976 Device cGMP were added
• Reason Problems with Dalkon Shield intrauterine
  devices were reported, and injuries resulted.
• 1997 21CFR11..!

Regulations are currently rather comprehensive..
however
10
Development of Regulations

• 2002 Pharmaceutical cGMPs for the 21st Century
  A Risk-Based Approach.
• Reason FDA thought regulations were becoming
  too developed and wanted the pharma industry to
  be able to take better advantage of advanced
  technologies.
• Changes to FDAs cGMPs to be expected in 2005.

11
Prevalence of computers

• Computers are used extensively across the entire
  pharma-product value chain

I am a patient
Discovery
Pre-clinical tests
Clinical tests
Manufacture, sales and distribution
I am monitoring the safety of our marketed
products
Every operation is supported or run by
computers
12
Computers add to the complexity!

• Computers are social beings they multiply
• Programs include more and more features
• Computers interconnect
• IT Infrastructures grow
• Computers open up for the world to see.

We must still provide documented assurance that
everythings under control and performs as
specified.
13
Functional environment
System specifications
Problem management
Operations instructions
training
System owner
Environments
Platform administrators
Critical parameters
Application experts
System administrator
Configuration item list
User manuals
Users
Suppliers
Technical support
revalidation
IT supporters
Auditors
audit reports
Descriptions of responsibilities
QA/Validation
System definition
AI-calibration
Service Level Agreements
Change requests
Data security
Admission control
Non-conformities
Qualification and validation documentation
logbook
security set-up
User requirements
System manuals
14
Responsibilities

• The pharma-firm is responsible for all aspects
  concerning their products safety, quality,
  purity, strength and identification.

• The pharma-firm cant blame it on someone else
• so it must take appropriate actions to ensure
  compliance.

• VALIDATION is the key word

15
Key validation elements

• Independent QA/QC involvement
• SOPS and documentation
• Life cycle oriented all phases
• Written and pre-approved plans
• High quality records to prove that plans were
  followed
• Configuration and Change Management
• User Access Controls
• Did I mention documentation?

Control and compliance!
16
Extent of Validation

• The extent of validation necessary will depend on
  a number of factors including the use to which
  the system is to be put, whether the validation
  is to be prospective or retrospective and whether
  or not novel elements are incorporated.
  Validation should be considered as part of the
  complete life cycle of a computer system. This
  cycle includes the stages of planning,
  specification, programming, testing,
  commissioning, documentation, operation,
  monitoring and modifying.

EUGood Manufacturing Practice
17
Suppliers now speak validatian!

• Facilitated by, eg.
• ISPE/GAMP-guides
• conferences
• customer/supplier interactions
• economic incentives?
• Suppliers are gradually becoming aware of
  validation requirements
• speak the same language
• if with an accent

18
How can suppliers further contribute to achieve
compliance and control?

• Pharma firms are inherently cautious as we might
  hurt the public physically or ourselves
  financially.
• Pharma firms need their suppliers to be familiar
  with the pharma domain and pertinent regulations.
• we cant inspect and test everything ourselves
• we must apply a risk based approach and ltsighgt
  rely on our suppliers to their part properly.

19
How can suppliers further contribute?

• We must maintain system life long, good working
  relationships with suppliers.
• keep an open dialog
• be as honest as possible
• learn and teach
• do on site audits from time to time
• But accept severance if shortcomings persist

20
How can suppliers further contribute?

• My personal wish for all computers intended for
  use in Novo Nordisk.
• Useful
• Robust
• Predictable
• Effective
• Secure
• Maintainable
• Scalable
• Well documented

21
Theres a happy QA-person ?
Thank you all and enjoy your lunch