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The needs for Quality system proceeds from a logical development of quality.

In the 1950-60, most of the pharmaceutical companies introduced specifications for their finished products and later on for their raw materials: that was QUALITY CONTROL. Controlling the product that goes out of the door was the state of the art. This was a good step forward to ensure the quality of the drugs delivered to customers.

In the 1980 emerged the concept of QUALITY ASSURANCE, when companies understood that just controlling what goes out of the door was right but was also costly; when results were out of specifications, it was often too late to act and the batch of product was already lost.
So they introduced preventative measures such as qualification, validation, suppliers’ management (agreement, audits), and metrology, to assess the quality of the elements entering in the manufacture of the drugs before the production.

Again this was right, but not enough, since it did not address the defects that were already incorporated into the product, during the development, such as bad specifications, wrong scale-up technology, inadequate stabilities, etc.
Quality was managed at a sub managerial level (maybe not officially, but effectively) and no clear vision of the quality of the products was available to the management.
Risk assessment was not used systematically to help with the prioritization of the activities.
And knowledge was not managed, wasting one of the major assets of the companies-… – knowledge.
Last but not least, the life cycle of the products was not taken in account from start of a project. The consequences of discontinuing a product were not adressed.

Then came ISO! ISO 9000! And 20 years later the pharmaceutical industry starts the implementation of QUALITY SYSTEMS!

We have built and managed Quality systems in
•    large pharmaceutical companies
•    small start-ups specialized in the development of products in the Pharmaceutical or Biotechnology sectors,

The activities started from the definition of the needs and the establishment of the necessary documentation, the implementation of the instructions by internal training and the review of the application of the systems by auditing.

We have also assisted

• a US company that wanted to build a site to manufacture cell therapy products in CH for its international markets.
• a start-up company that wanted to start clinical investigations in Europe.
• a biotechnology company offering cGMP manufaturing services to clients
• a US company building its distribution centre in Europe
• an R&D company to run its audit program

When the structure of the Quality System has been set, the tools need to be built to make the system alive.

The quality objectives are defined based on the Quality Policy and the risk analysis for the specific situation of the company. The Quality Manual, the Policies, the Sops follow the documents management process and when approved are taught to the concerned employees and implemented.

Documents need to be managed to show the level of control that the company has on its projects and products.

Qualifications, Validations, Calibrations have to be planned and carried out.

The third parties are controlled and audited as required. Internal inspections are run and the results documented in the next quality plan.

Investigations tools (CAPA) are prepared to deal with deviations.

Batch release follow a well defined process. 

The company is prepared for regulatory inspections.

We have presented Quality System philosophy to management, built >20 different Quality Systems.

We have written Quality Manuals, Policies, 100th of SOPs.

We have prepared Qualification / Validation plans.

We have trained managers and operators to GMP.

We have trained investigators to GCP.

We have audited > 200 GMP, GLP and GCP sites (see audits)

Auditing is the eyes of the quality system. Your system will be as good as your looking at it.
Need GOOGLES?

Auditing is a specialized activity that can be regarded from different angles.

From the contract giver window, auditing is verification that the contract acceptor performs correctly the tasks described in the agreement.

From the contract acceptor window, it is a burden that is necessary to satisfy the contract giver … or it could be … a cost free (almost) assessment of its capacities to be competitive, replacing expensive evaluations by external experts?

The observations reported by the auditors have to be corrected on time, in order to avoid
•    that the complete operations are compromised or worth,
•    conduct to unsatisfactory studies or products or worth
•    place the patients at risk!

The independence of the auditor can be an asset to avoid the “Conflict of Interest” problematic.

We are recognized auditors of the following activities

GMP (over 150 sites):
•    Active ingredient
•    Drug product under
o    solid,
o    liquid,
o    semisolid,
o    aseptic forms
•    GDP

GLP (over 30 sites)

GCP (over 50 sites):
•    CROs
•    Clinical trial sites
•    Vendors (data management, Laboratories

Correcting the designs of a planned new site can be done in hours. Correcting a new site because it was not realized according to the requirements needs months.

Our experience of planning the activities necessary to build new pharmaceutical sites shows that the design qualification is the key part of the engineering process.

The process, the equipments, the facilities, the utilities have to be optimized to deliver a product which is satisfactory and competitive.

To achieve this, the knowledge of chemical / biotechnological / pharmaceutical processes and the engineering techniques is the key determining factor.

We have prepared design qualification for sites producing

•    solids in a large pharmaceutical plant,
•    biotechnology products for clinical trials
•    cell therapy products
•    pharmaceutical laboratories for small scale production (hospital pharmacies)

We also have built class A to D clean rooms to manufacture biotechnological IMPs.

The realization of the facilities is performed in close cooperation with a renowned architect and specialists of the building matters.

The Biotech and the Pharmaceutical industries use more and more transport of products by the cold chain or temperature-controlled chain. The reliability of this mode of transport is variable, temperature excursions happening in 1 to 5% of the cases.

The control of the transport conditions is critical, since even if the transport pack is validated, no one can predict the actual delivery conditions of the pack within the predetermined period and within the predetermined validated temperature range. A control with temperature sensors is necessary and the consequences of temperature excursions have to be evaluated in advance.

The delivery of packs between the partners of the distribution chain is just one aspect of the transport of products by the temperature controlled chain. The other aspect is the transport … and the use of the product from the last step of the distribution chain to the final user. In this part, there is presently a lack of real leadership by the pharmaceutical industry.

How to determine that the patient receives really the product in its genuine status and uses it when it is still in its conditions specified to retain the safety, efficacy and quality characteristics?

We have defined a new methodology to evaluate temperature excursions as they may occur during the transport of medicinal products by the cold or temperature controlled chain.

The standard methods are focused on the measurement of temperature and assessment of its deviations. It is right that  temperature is the source of potential degradation of the product. But the real goal is to check if the product itself was degraded at an unacceptable value.

For more information, please

• contact us or
• read the article A mathematical approach to assessing temperature excursions in temperature-controlled chains, Claude Ammann, European Journal of Parenteral & Pharmaceutical Sciences 2008; 13(2): 57-59

Abstract: More and more products are distributed by the temperature-controlled chain. It can happen that products are subject to temperature excursions. The decision to release them is often based on subjective arguments. This paper presents a mathematical model that could be used to assess the temperature excursion effect on the potency of the product.

or

• Stability Studies Needed to Define the Handling and Transport Conditions of Sensitive Pharmaceutical or Biotechnological Products, Claude Ammann, AAPS PharmSciTech (2011)

Abstract: Many pharmaceutical or biotechnological products require transport using temperature controlled systems to keep their therapeutic properties. There are presently no official guidelines for testing pharmaceutical products in order to define suitable transport specifications. After reviewing the current guidance documents, this paper proposes a methodology for testing pharmaceutical products and defining appropriate transport conditions.