Process Validation Stage 1: Parenteral Process Design

Process validation is the most critical regulatory requirement for licensed biopharmaceuticals and vaccine facilities. It is also considered as an economic issue through understanding and controlling any process and subsequently minimizing the processes failures. The process design (PD), process qualification (PQ) and continued process verification (PV) are the main three stages for industry for process validation. It was defined as the collection and evaluation of data, from the process design stage throughout production, to establishe a scientific evidence that a process is consistently delivering high quality products and in accordance with the principles of Good Manufacturing Practice (GMP). The challenges of vaccine production process are not limited to its complicated details which may change the validity of the process but also the cross process that still the biggest challenge. Therefore, process validation in biopharmaceutical industries has the high priority specially vaccine production. In conclusion, continuous monitoring and validation of inactivated veterinary vaccines has the great impact on defects, nonconformance decreasing and processes improvement. Also the critical parameters of process validation of inactivated veterinary vaccine manufacturing are highlighted.

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Recommended Best Practices for Lyophilization Validation 2021 Part II: Process Qualification and Continued Process Verification

AAPS PharmSciTech ◽

10.1208/s12249-021-02107-6 ◽

2021 ◽

Vol 22 (8) ◽

Author(s):

Feroz Jameel ◽

Alina Alexeenko ◽

Akhilesh Bhambhani ◽

Gregory Sacha ◽

Tong Zhu ◽

...

Keyword(s):

Best Practices ◽

Process Design ◽

Control Charts ◽

Batch Size ◽

Drying Time ◽

Process Validation ◽

Process Verification ◽

Process Qualification ◽

The Impact ◽

Validation Strategy

Abstract This work describes the lyophilization process validation and consists of two parts. Part one (Part I: Process Design and Modeling) focuses on the process design and is described in the previous paper, while the current paper is devoted to process qualification and continued process verification. The goal of the study is to show the cutting edge of lyophilization validation based on the integrated community-based opinion and the industrial perspective. This study presents best practices for batch size determination and includes the effect of batch size on drying time, process parameters selection strategies, and batch size overage to compensate for losses during production. It also includes sampling strategies to demonstrate batch uniformity as well as the use of statistical models to ensure adequate sampling. Based on the LyoHUB member organizations survey, the best practices in determining the number of PPQ runs are developed including the bracketing approach with minimum and maximum loads. Standard practice around CQA and CPP selection is outlined and shows the advantages of using control charts and run charts for process trending and quality control. The case studies demonstrating the validation strategy for monoclonal antibody and the impact of the loading process on the lyophilization cycle and product quality as well as the special case of lyophilization for dual-chamber cartridge system are chosen to illustrate the process validation. The standard practices in the validation of the lyophilization process, special lyophilization processes, and their impact on the validation strategy are discussed. Graphical Abstract

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Design of objective lens for 200-kV high-resolution electron microscopes

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100075361 ◽

1983 ◽

Vol 41 ◽

pp. 314-315

Author(s):

K. Tsuno ◽

T. Honda ◽

Y. Harada ◽

M. Naruse

Keyword(s):

Optical Properties ◽

Computer Technology ◽

Axial Magnetic Field ◽

Chromatic Aberration ◽

Objective Lens ◽

Resolution Electron ◽

Correction Of Astigmatism ◽

Three Stages ◽

Electron Microscopes ◽

Stage 1

Developement of computer technology provides much improvements on electron microscopy, such as simulation of images, reconstruction of images and automatic controll of microscopes (auto-focussing and auto-correction of astigmatism) and design of electron microscope lenses by using a finite element method (FEM). In this investigation, procedures for simulating the optical properties of objective lenses of HREM and the characteristics of the new lens for HREM at 200 kV are described.The process for designing the objective lens is divided into three stages. Stage 1 is the process for estimating the optical properties of the lens. Firstly, calculation by FEM is made for simulating the axial magnetic field distributions Bzc of the lens. Secondly, electron ray trajectory is numerically calculated by using Bzc. And lastly, using Bzc and ray trajectory, spherical and chromatic aberration coefficients Cs and Cc are numerically calculated. Above calculations are repeated by changing the shape of lens until! to find an optimum aberration coefficients.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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