Guide to Inspections of Lyophilization of Parenterals (Fda Inspection Guidelines) on *FREE* shipping on qualifying offers. Appendix D: Guide to Inspections of Lyophilization of Parenterals. William M. (Bill ) Huitt ยท Search for more papers by this author. Book Author(s). GUIDE TO INSPECTIONS OF LYOPHILIZATION OF PARENTERALS Note: This document is reference material for investigators and other FDA personnel. The.

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It is well recognized that people are the major source of contamination in an aseptic processing filling operation. Because product will dry from the top down, the tip of the thermocouple should always be placed at the very bottom and center of the container.

Freeze Drying / Lyophilization Information: Basic Principles

Product is either pre-loaded into vials which are then transferred to the shelf or it is loaded in bulk form directly onto a product tray. Each manufacturing facility is an ISO Significant regulatory situations have resulted when some manufacturers have hand-stoppered vials. Manufacturers are actively sampling the surfaces of personnel working in aseptic processing areas. Food and Drug Administration. These products can benefit from a thermal treatment process, which is also called annealing.

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Guide to inspections of lyophilization of parenterals [microform] | National Library of Australia

The refrigeration system cools the ice condenser located inside the freeze dryer. The sterilization of condensers is also a major issue that warrants discussion. At the end of primary drying when all of the free ice crystals have been sublimed, the product will appear to be dried.


Probably more so than any other product, scale-up of the lyophilization cycle is very difficult. In an effort to identify the particular sections of lyophioization and aseptic manipulation that might introduce contamination, several manufacturers have resorted to expanded parentwrals fills.

Typically, operator involvement in a computer controlled lyophilization cycle primarily occurs at the beginning. When the vacuum level set point is deeper than the vapor pressure of ice at the current product temperature, sublimation can take place.

There are some atypical filling operations which have not been discussed. When this valve is closed the chamber is isolated from the external condenser. The condenser temperature inspectipns is dictated by the guixe point and collapse temperature of the product. Determination of the critical collapse temperature of a product is an important step in establishing and optimizing a freeze drying process.

On some occasions, manufacturers have established expiration dates without performing label claim reconstitution potency assays at the various test intervals and particularly the expiration date test interval.

We are recognized experts in applications, methodologies, lab processes and many other inspectios that directly impact your day-to-day operations.

When the target product temperature is obtained, the shelf temperature is held constant for the balance of primary drying.

These may result in greater instability and increased product degradation. Obviously, the manufacturer should know the eutectic point and have the necessary instrumentation to assure the uniformity of product temperatures. The USP points out that compendial standards apply at any time in the life of the article.

For example, the presence of Pseudomonas sp. When sublimation of ice crystals is complete, the product temperature will increase and approach the shelf temperature. More than a scientific equipment supplier, SP Scientific represents brands that distinguish themselves by being able to more thoroughly assist customers in matching equipment to particular application needs.


Thus, there could be some ethylene oxide in the nitrogen supply line during the backfilling step. A controlled change of the product pwrenterals as a function of time, during the freezing process, so as to ensure a completely frozen form. It is recognized that there is complex technology associated with the manufacture and control of a lyophilized pharmaceutical dosage form. Read the Text Version. Pardnterals Scientific service professionals are highly knowledgeable and are qualified to support every instrument, software and application product that SP Scientific has brought to the market.

Another major concern with the filling operation is assurance of fill volumes. System pressures in the mTorr to mTorr range will usually promote an adequate amount of convection. This is the water that is removed desorbed during secondary drying.

Basic Principles of Freeze Drying

Because shelf contact is often inconsistent, convective heat transfer can help promote uniform product drying. That is, they have filled approximately vials during a media fill and segmented the fill into three stages. The initial phase provides for sterilization of the shelves when they are separated.

It is not recommended to arbitrarily and repetitively increase the shelf temperature during primary drying, as is seen on some older legacy cycles. Merely testing samples after the lyophilization cycle is concluded may be insufficient to justify the release of the remaining units. When there are problems with the systems in the lyophillzation, contamination could migrate from the condenser back to the chamber.

There have been some situations in which manufacturers have loaded the dosage units on metal trays which were not removed.