Publications Archives - Sajjadi Consulting

Upcoming Publication: Practical Considerations in Using an Equivalence Approach to Establish Lot Release Limits for Vector Dose

BioProcessing Journal has invited Dr. Janice Callahan and I to publish a second manuscript as a follow-on to a prior publication proposing an equivalence model for lot release and vector dose assignment. This preview of the work-in-progress…

Defining Therapeutic Window for Viral Vectors: A Statistical Framework to Improve Consistency in Assigning Product Dose Values

Publications

This open access article was co-authored with my statistical consultant colleague of 30+ years. In it we propose using an equivalence approach for lot release testing of vector products. Because dose related toxicity is a concern, dose assays…

Assessing parallelism prior to Determining Relative Potency

Publications

With nearly 50 citations, this paper summarizes the unanimous agreement of a USP committee, that the method for assessing parallelism that is currently presented in 〈111〉 and in the European Pharmacopeia's Chapter 5.3 is flawed and should…

Phase 1 trial of FVIII gene transfer for severe hemophilia A using a retroviral construct administered by peripheral intravenous infusion

Publications

This paper, cited over 200 times, summarizes a phase 1 dose escalation study, 13 subjects with hemophilia A received by peripheral intravenous infusion a retroviral vector carrying a B-domain–deleted human factor VIII (hFVIII) gene. This was…

Defining a Detailed Approach to Using the Adenovirus Reference Material (ARM)

Publications

This white paper encouraged advocates of the adenovirus standard to carefully examine its use in the field. It was originally presented at conference in 2003 but the article has recently been made open access (https://www.bioprocessingjournal.com/afp/J25-Sajjadi.pdf)…

Analysis of testes and semen from rabbits treated by intravenous injection with a retroviral vector encoding the human factor VIII gene: no evidence of germ line transduction

Publications

In this paper, we demonstrated that a PCR assay to detect vector was fit for its intended purpose. In collaboration with Kim Boekelheide at Brown University, my group addressed a key regulatory concern for integrating vectors- potential for…

Working toward an adenoviral vector testing standard

Publications

This paper summarizes the proceedings of a conference held to discuss the development of an adenoviral vector standard. In response to the tragic death of Jesse Gelsinger, dose related toxicity became a focus in the field of gene therapy.…

Generation of retroviral packaging and producer cell lines for large-scale vector production and clinical application: improved safety and high titer

Publications

This paper, cited 70 times, describes improvements in retroviral vector packaging and producer cell lines designed to yield higher unprocessed manufacturing titers, complement-resistant vectors, and minimize the potential to generate replication-competent …

Development of retroviral‐based gene therapy products: a quality control perspective

Publications

This early article provided a broad overview and a brief history of quality control considerations in the development of retroviral-based gene therapy products. As part of pioneering efforts in the field and early regulatory experience, I…

Evaluation of PCR and ELISA assays for screening clinical trial subjects for replication-competent retrovirus

Publications

This paper is cited as reference #30 in the FDA’s 2020 guidance on Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up https://www.fda.gov/media/113790/download …

Anti-vector immunoglobulin induced by retroviral vectors

Publications

This paper summarizes work to character vector immunogenicity. Studies showed that intramuscular (i.m.) administration of retroviral vector induces strong anti-vector Ig responses, in a dose-dependent fashion. Although such anti-vector Ig was…

Evidence for localization of biologically active recombinant retroviral vector to lymph nodes in mice injected intramuscularly.

Publications

Results of these studies indicated that the localization of retroviral DNA to the injection site and regional lymph nodes may play a role in the induction of the product directed, specific CTL responses detected in splenocyte populations isolated…

Recombinant retroviral vector interferes with the detection of amphotropic replication competent retrovirus in standard culture assays

Publications

This paper has been cited over 40 times. It summarizes studies that revealed that recombinant retroviral vector can interfere with the detection of low-level RCR in culture and that such interference can be partially overcome by culturing…

Recombinant retroviral vector delivered intramuscularly localizes to the site of injection in mice

Publications

Two of the main safety considerations associated with the direct administration of recombinant retrovirus are the generation of replication-competent retrovirus in vector-producing cell lines and inadvertent germ-line transduction. In this early…